Saturday, 2 November 2013

Cerebritis, Lupus, and Lupus Cerebritis

Cerebritis is defined as an inflammation of the cerebrum, a structure associated with memory, speech, etc., as a result of the formation of an abscess within the brain itself, found commonly in patients with lupus.

Systemic lupus erythematosus (SLE) or Lupus is a chronic, autoimmune disease as as a result of the development of autoantibodies that attack the systems and organs in the body.researchers at the indicated that saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production.

Lupus cerebritis is a disorder of nervous system problems (an autoimmune inflammatory disorder) caused by lupus as as a result of the development of autoantibodies that attack the systems and organs in the body. It causes migraine headache, if the duration of the central nervous system involvement last for a few minutes, or causes dementia that can lead to neurological deficits as a transient attacks or permanently.

A. Symptoms
Common symptoms include
1. Slurred speech
2. Confusion
3. Nausea and dizziness
4. Visual disturbances
5. Mood changes
6. Memory loss
7. Swelling
8.  Headaches, depression, anxiety
9.  Seizures
10. However, symptoms of cerebritis in some cases can evolve and worsen quickly as patients may develop severe and life-threatening conditions including stroke and heart-related death-causing diseases.
11. Etc.

B. Causes
Cerebritis can be caused by an infection due to bacteria, viruses invasion and pathogens invasion into
the brain through the sinuses or as a result of trauma
1. Gene
Research at the Oklahoma Medical Research Foundation, published in the April 6 issue of the American Journal of Human Genetics describes three lupus genes discovered by OMRF researchers as part of a massive international collaboration, by Using samples from a wide range of ethnic backgrounds, scientists found the genes IRF8 and TMEM39a were associated with lupus in European-American, African-American, Gullah and Asian patients. A third gene named IKZF3 was only significant in African-American and European-American samples."Identifying and characterizing these genetic risk factors in lupus will undoubtedly lead to improved diagnostics and therapeutics for this complex disease," said senior author and OMRF scientist Kathy Moser, Ph.D.(18)

2. Klebsiella pneumoniae
Klebsiella pneumoniae is defined as a form of bacterial pneumonia associated with Klebsiella pneumoniae. In a report of a case of Klebsiella cerebritis in an adult patient with a proven extracranial focus of infection, researchers suggested considering cerebritis as a differential diagnosis for altered level of consciousness in patients of severe sepsis, even if an extracranial source of infection is proven.(2)

3. Autoimmune system dysfunction
Some researchers found that the interactions between elevations of serum prolactin (PRL)[1], cytoquines[2], autoantibodies[3] and organ involvement[4] suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in systemic lupus erythematosus (SLE), will help us to understand and treat this important autoimmune disease(3)

[1]. Elevations of serum prolactin (PRL)
In a study of conducted by Centro Medico Nacional La Raza, showed that elevated PRL and interleukin (IL)-6[5] have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE.(3)

[2]. Cytoquines
Cytoquines is a small protein released by cells that has a specific effect on the interactions between cells, on communications between cell, or on the behavior of cells. There a report that the final mechanism of lupus cerebritis involves the cytokines. The cytokines trigger edema, endothelial thickening, and infiltration of neutrophils in brain tissue. Two cytokines, interferon alpha and interleukin-6, have been found in the CSF of SLE patients with psychosis(4)

[3}. Antibodies
In the study to investigate the possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA) antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id, respectively) were expressed on anti-DNA antibodies during a subsequent active period (9/90) of the disease, researchers at the St. Luke's Hospital showed that they are of related clonal origin. The present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the shift of antigen specificity within an idiotypically related anti-DNA population during exacerbation of the disease.(7)

[4] Organ involvement
In the report there are few data on the relationship between the onset of new organ involvement and lupus serologies, especially in children, found that in managing two children with lupus nephritis, both developed life-threatening extrarenal complications (cerebritis and carditis) soon after receiving high-dose immunosuppressive therapy and despite normalizing serologies. This lack of concordance between serologies and the development of carditis and cerebritis needs to be recognized so that health care professionals treating children with SLE can promptly intensify immunosuppressive medications and avoid life-threatening delays from seeking alternative explanations for symptomatology.(5)

[5]. Interleukin (IL)-6
Interleukin (IL)-6 secreted by T cells and macrophages to stimulate immune response has the function to act  both a pro-inflammatory and anti-inflammatory cytokine.[see Cytoquines]

[6]. DNA and anti-DNA complexes
Circulating immune complexes, consist of DNA and anti-DNA, cause an inflammatory response as well as a disruption of the blood-brain barrier. There is a report that the number of patients with the SLE manifestations was not higher in the group with the high amount of DNA in immune complexes. Elevated levels of DNA in immune complexes was found only in sera of SLE patients with the active, as well as quiescent form, of the disease and not in sera of healthy donors. The presence of increased amounts of DNA antigen in circulating immune complexes could indicate the presence of SLE pathology even if no manifestations of SLE are found.(6)

[7]. Etc.

C. risk factors
1.  Ultraviolet light 
exposure to ultraviolet light increases the risk of as it can exacerbate lupus by modulation of the immune system at the level of the skin. It has also been found that ultraviolet light can lead to the formation of antinuclear antibodies.(8)

2. Pegylated interferon therapy
People who are in treatment with  receiving pegylated interferon monotherapy may increase the risk of Lupus activation with cerebritis(9)

3. Gene mutation 
An international team of researchers led by Chaim O. Jacob, associate professor of medicine and microbiology & immunology at the Keck School of Medicine of USC, has identified a gene mutation involved in causing lupus, a chronic inflammatory disease that affects the skin, joints and organs, posted in the Dec. 26 online edition of the Proceedings of the National Academy of Sciences.(19)

4. Other risk factors
Risk factors were more present in bacterial infections of the nervous system and cerebrit than in virus infection of CNS. In virus infections of the CNS, 28% of patients had some risk factor, most often-chronic ethylism[1], diabetes mellitus[2] and acquired heart diseases[3]. In bacterial infections of the CNS, 64% of patients had some predisposed factor. The most frequent factor of risk in these patients were chronic otitis[4] (21.6%) and cranio-trauma[5] (14.4%). In cerebritis, risk factors were present in 76% of patients and they were: sepsis[6] (20%), chronic otitis[7] (12%) and systemic lupus erythematosus[8] (8%).(10)

Diagnosis
There is no specific standard for the diagnosis, bur some researchers suggested
the following
1. Serologic tests
Is the test to measure the levels of specific antibodies in a patient's blood, the test is essential as the antinuclear antibody (ANA) titer is positive in virtually all patients with this disorder, but some researchers showed that serologic tests are helpful in establishing the diagnosis of SLE and predicting disease flares. However, there are few data on the relationship between the onset of new organ involvement and lupus serologies, especially in children.(11)

2. Electroencephalography (EEG) 
Electroencephalography (EEG) is to record the measurement of voltage fluctuations resulting from ionic current flows within the neurons of the brain. In a report of a 13-year-old girl with a known diagnosis of systemic lupus erythematosus presented with seizures and psychosis. An electroencephalogram (EEG) revealed continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in the left temporal region, which did not resolve with benzodiazepine. A magnetic resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the left medial temporal and left occipital lobes, left thalamus and bilateral cerebellar white matter, with evidence of vasculitis in the magnetic resonance angiography. Intravenous immunoglobulin was given because of failed steroid therapy, which resulted in a full resolution of clinical, EEG and MRI abnormalities. Lupus cerebritis should be considered as a possible aetiology in (Focal (Nonepileptic) Abnormalities on EEG) PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.(14)

3. Computed tomography (CT scans)
In the study of thirty-four patients from the Jackson Memorial Hospital and Miami Veterans Administration Medical Center complex with 4 or more ARA criteria for SLE had CT of the brain. Of these patients with SLE, 14 had clinical features of cerebritis and 20 without cerebritis on longterm steroid therapy served as controls. Clinical examinations were performed by 1 of our group (NG). The CT of the brain was independently read by 2 neuroradiologists (SO and RQ), whose only knowledge of the patients was their age, sex and the diagnosis of SLE, showed that some abnormality of the brain by CT was present in 11/14 patients during their 1st attack of SLE cerebritis. At the initial presentation with SLE cerebritis, 9 of 14 patients had marked cortical atrophy by CT and 2 had minimal cortical atrophy. At that time, a normal CT was found on 3 patients with SLE cerebritis. Two of these patients were on 30 and 40 mg prednisone at the time of the normal CT. The 3rd had been on corticosteroids previously but not in 4 months prior to the normal CT. Corticosteroids were administered in all 3 patients and after remission and reexacerbation of SLE cerebritis, repeat CT demonstrated development of marked cortical atrophy in 2 of these patients and minimal cortical atrophy in the other. The role of corticosteroids in their cortical atrophy is unclear.(12)


4. A magnetic resonance imaging (MRI)
Most systemic lupus erythematosus patients having central nervous system involvement tend to have abnormal MRI scans, as cerebral edema that can occur due to cerebritis can be effectively identified by MRI scan(13) 

5. Etc. 

Prevention
A. What to avoid
Any thing which cause inflammation must be avoid. thyere is a report found that SLE patients and lupus-prone mice induces skin inflammation following intradermal injection into normal mice. Lupus serum depleted of IgG failed to cause skin inflammation(36). including
1. Sugar
Refined sugar with high glycemic values cause fluctuation of insulin levels and put the immune system on high alert. In the evaluation of one hundred and eleven serum samples were assayed from patients with Graves' disease, primary hypothyroidism, chronic autoimmune thyroiditis, Addison's disease, chronic autoimmune hepatitis, pernicious anemia, lupus erythematosus, and rheumatoid arthritis, together with 45 serum samples from normal subjects, conducted by Clinic of Endocrinology, University La Sapienza, showed that contrary to expectation anti-immunoglobulin antibodies are not associated with non-diabetes-related autoimmune diseases, increased humoral immunoresponsiveness to endogenous insulin appears to be related to autoimmunity in general rather than restricted to Type I diabetes.(33)

2. Saturated and trans fat
Saturated fat and trans fat  trigger and stimulate the immune system's inflammatory response. In the study of Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling, Dr. Haitao Wen, and the team indicated that High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome(34)
3. Diary products
Diary products can cause allerdic effect that lead to the production immunoglobulin E antibodies, histamine, etc., causing immune system malfunction.

4. Process foods
In an article of Inflammatory Foods, Consider avoiding to achieve Natural remission in RA, the author wrote "often times people reduce the intake of inflammatory foods but fail to recognize all the hidden places, generally in processed foods, that these foods are being consumed. Many arthritic symptoms are triggered by allergies" (35) that can lead to inflammation.

5. Smoking and alcohol
In the assessment of whether smoking or alcohol consumption is associated with lupus erythematosus (LE), conducted by Place de l'hôpital, Dr. Boeckler P and the team showed that cigarette smoking is associated with LE, but alcohol consumption is not. The risk conferred by cigarette smoking seems highest in patients who meet fewer than 4 ACR criteria and/or who do not have antinuclear DNA antibodies(37)

6. Refined products
Refined grains pattern was positively related to sICAM-1 (P for trend = 0.007)(38)

7. Artificial ingredients
There is a report that scientists disagree about the relationships between sweeteners and lymphomas, leukemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkinson's disease, Alzheimer's disease, multiple sclerosis, autism, and systemic lupus.(39)


8. Allergic effects
Allergic effect can increase the risk of the development of lupus as a result of inflammation caused by  immune system malfunction.


9. Etc.


B. Diet against Lupus
1. Deep see fish (such as Salmon)(24)
a. Antioxidants
In the research of the antioxidant effect of vitamin E after ingestion of salmon found that that megadoses of vitamin E, far from having pro-oxidative activity, actually increase the anti-oxidative capacity of the liver, especially after ingestion of salmon oil, according to "Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil" by Flader D, Brandsch C, Hirche F, Eder K.(e)

b. Vitamin D
Vitamin D not only is important to the heart health with calcium supplementation, according to "Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular event` by Wang L, Manson JE, Song Y, Sesso HD.(Ia) but also plays an vital role in epidemiological associations between vitamin D status and a large number of autoimmune and inflammatory diseases, according to "Vitamin D and inflammation" by Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC.(I)

c. Omega 3 fatty acids
Omega 3 fatty acids is necessary to maintain the ratio of good and bad cholesterol, thus reducing the risk of cholesterol inflammation according to the study of "In vitro fatty acid enrichment of macrophages alters inflammatory response and net cholesterol accumulation" by Wang S, Wu D, Lamon-Fava S, Matthan NR, Honda KL, Lichtenstein AH., posted in PubMed (IV) and forming of free radical in the heart cells, leading to heart diseases. It also reduces the risk of plaque forming in the arterial wall, thus also decreasing the risk of stoke, according to the study of "N-3 vs. saturated fatty acids: effects on the arterial wall" by by Sudheendran S, Chang CC, Deckelbaum RJ.

d. Anti inflammationIt is said the Omega 3 fatty acids beside reduced the risk of inflammatory effects on our joints and improved blood flow, by regulating the migration of inflammatory cells that cause inflammation, but also autoimmune diseases as a result of the elevation of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids, according to the study of "Omega-3 fatty acids in inflammation and autoimmune diseases" by Simopoulos AP.

e. Etc.


2. Olive oil(25)
a.  Antioxidants and weight loss
In the
analyzing the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity (TAC) found that Mediterranean diet, especially rich in virgin olive oil, is associated with higher levels of plasma antioxidant capacity. Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil, according to "A 3 years follow-up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain" by Razquin C, Martinez JA, Martinez-Gonzalez MA, Mitjavila MT, Estruch R, Marti A.(c)

b. Free radical
Oleic acid contains high amount of andioxidant that helps to improve the immune system in fighting against the forming of free radicals cause of lipid peroxidation , according to "Effect of dietary high-oleic-acid oils that are rich in antioxidants on microsomal lipid peroxidation in rats" by Perona JS, Arcemis C, Ruiz-Gutierrez V, Catalá A.

3. Romaine Lettuce(26)
a. Antineurodegenerative effect
In the investigation of Phenolics extracted in fresh romaine lettuce and its effect on on biological protection for neuron-like PC-12 cells found that total phenolics and total antioxidant capacity of 100 g of fresh romaine lettuce averaged 22.7 mg of gallic acid equivalents and 31.0 mg of vitamin C equivalents, respectively. The phenolic extract of romaine lettuce protected PC-12 cells against oxidative stress caused by H(2)O(2) in a dose-dependent manner. Isochlorogenic acid, one of the phenolics in romaine lettuce, showed stronger neuroprotection than the other three caffeic acid derivatives also found in the lettuce, according to "Antineurodegenerative effect of phenolic extracts and caffeic acid derivatives in romaine lettuce on neuron-like PC-12 cells" by Im SE, Yoon H, Nam TG, Heo HJ, Lee CY, Kim DO.

b. Antioxidants
In the evaluation of phenolic extracts from lettuce (baby, romaine, and iceberg cultivars) and their antioxidants effect found that the antioxidant capacity was linearly correlated with the phenolic content. The results obtained indicate that lettuce byproducts could be, from the industrial point of view, an interesting and cheap source of antioxidant phenolic extracts to funcionalize foodstuffs, according to "Lettuce and chicory byproducts as a source of antioxidant phenolic extracts" by Llorach R, Tomás-Barberán FA, Ferreres F.

c. Chlorophyll
Chlorophyll is a green pigment found in almost all plants, algae, and cyanobacteria, including romaine lettuce. It has anti-oxidant, anti-inflammatory, body cleansing and wound-healing properties, according to the study of "Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers" Jubert C, Mata J, Bench G, Dashwood R, Pereira C, Tracewell W, Turteltaub K, Williams D, Bailey G., posted in PubMed (40) researchers wrote that Chlorophyll (Chla) and chlorophyllin (CHL) were shown previously to reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats.
 
4. Tomato(27)
a. Antioxidative and Cancer Cell-Inhibiting Activities
In the research of Tomato ( Solanum lycopersicum ) plants synthesize nutrients, pigments, and bioactive compounds and their benefit in nutrition and human health found that Tomato extracts promoted growth in normal liver (Chang) cells, had little effect in normal lung (Hel299) cells, mildly inhibited growth of lung cancer (A549) cells, and first promoted and then, at higher concentrations, inhibited growth in lymphoma (U937) cells. The relationship of cell growth to measured constituents was not apparent, according to "Free Amino Acid and Phenolic Contents and Antioxidative and Cancer Cell-Inhibiting Activities of Extracts of 11 Greenhouse-Grown Tomato Varieties and 13 Tomato-Based Foods" by Choi SH, Kim HR, Kim HJ, Lee IS, Kozukue N, Levin CE, Friedman M.

b. Lycopene
Lycopene, one of the powerful antioxidant in tomatoes, not only helps the immune system in neutralizing the forming of free radicals in the body and according to Harvard investigation as it found that men who ate more than 10 servings tomato-based foods daily (like cooked tomatoes and tomato sauce,) had a 35 percent lower risk of developing prostate cancer than those who ate the least amount of these foods. The benefits of lycopene was more pronounced with advanced stages of prostate cancer. Also according to the study of "Chemoprevention of prostate cancer with lycopene in the TRAMP model" by Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M, Said JW, Heber D, Cohen P, Aronson WJ., posted in PubMed (41)

c. Antiseptic
Tomato is considered as antiseptic natural foods including natural antiseptic agent ascorbic acid that helps to enhance the immune system in guarding our body against the possibility of infection, sepsis, or putrefaction, according to the article of "The 7 Benefits Of Drinking Lemon Water" posted in Simple Health Cures.(42)

5. Calciferous vegetable (such as Cabbage)(28)
a. DNA Damage
Ascorbic acid (AA), known as vitamin C, has important antioxidant vitamin has exerted the activity in preventing (imazalil)IMA-induced cause of DNA damage, according to the stuyd of "The protective role of ascorbic acid on imazalil-induced genetic damage assessed by the cytogenetic tests' by Türkez H, Aydin E.


b.  Omega 3 fatty acid
Cabbage reduces the risk of cardiovascular diseases by controlling the secretion of bad cholesterol, due to high amount of Omega 3 fatty acid, according to the study of "The Omega-3 Index as a risk factor for cardiovascular diseases' by von Schacky C.(9)

6. Blueberries(29)
a.  Antioxidant Capacity
In the investigation of
Blueberry and blackberry wines commercially available in Illinois and theirs potential health benefits, found that fruit wines made from blueberries and blackberries may have potential health applications and therefore could contribute to the economy of the wine industry. Practical Application: The majority of wines are produced from grapes, but wine can also be produced from other fruits including blueberries and blackberries, which contain phenolic compounds that may contribute to human health, according to "Comparison of Chemical Composition and Antioxidant Capacity of Commercially Available Blueberry and Blackberry Wines in Illinois" by Johnson MH, Gonzalez de Mejia E.

b. DNA Damage
Ascorbic acid (AA), known as vitamin C, has important antioxidant vitamin has exerted the activity in preventing (imazalil)IMA-induced cause of DNA damage, according to the stuyd of "The protective role of ascorbic acid on imazalil-induced genetic damage assessed by the cytogenetic tests' by Türkez H, Aydin E.(2)



7. Tumeric(30)
c. Anti inflammatory effects
In a systematic review of the literature was to summarize the literature on the safety and anti-inflammatory activity of curcumin, found that curcumin has been demonstrated to be safe in six human trials and has demonstrated anti-inflammatory activity. It may exert its anti-inflammatory activity by inhibition of a number of different molecules that play a role in inflammation, according to "Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa)" by Chainani-Wu N.

b. Antioxidants
In the research of a literature search (PubMed) of almost 1500 papers dealing with curcumin, most from recent years, with ll available abstracts were read and pproximately 300 full papers were reviewed, found that curcumin, a component of turmeric, has been shown to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFkappaB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases, "Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases" by Bengmark S.

c. Neuroprotective effect
In the finding of the A Potential Neuroprotective Agent in treating Parkinson's Disease, found that curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD, according to "Curcumin: A Potential Neuroprotective Agent in Parkinson's Disease" by Mythri RB, Bharath MS.

8. Ginger (31)
GINGER for OSTEOARTHRITIS:Ginger has a thytochemical called curcumin that helps reduce inflammation. It helps to protect your joints.Before we go further, we would like to remind you of cautions of using Superfood GINGER. While GINGER can help to strengthen anticoagulants such as heparin, warfarin and ticlopidine by helping your blood get less sticky but ginger raises the odd of bleeding.

9. Garlic(32)
Garlic to fight COLD and FLU. The natural compoud Allicin is released when garlic is crushed. Allicin works to fight cold, flu and other infections by breaking down into smaller chemicals called Sulfur compounds. They wake up your inmuune system, helping your body to get rid of toxins and microorganisms naturally.

10. Etc.



C. Nutritional supplement against lupus
C.1. Free radical scavengers(20)
1. Bilirubin
Bilirubin is a prosthetic group which helps to break down molecules into smaller units in releasing energy, excreted in bile and urine. It is a cellular antioxidant, by reverting to biliverdin, a green tetrapyrrolic bile pigment, once again when oxidized that inhibits the effects of mutagens.

2. Carotenoids
Carotenoids are organic pigments, occurring in the chloroplasts and chromoplasts of plants and some other photosynthetic organisms like algae, some bacteria.
a. Beta-carotene
Beta-Carotene, an organic compound and classified as a terpenoid, a strongly-coloured red-orange pigment in plants and fruits.
a.1. It is not toxic and stored in liver for the production of vitamin A that inhibits cancer cell in experiment. Beta-carotene also neutralize singlet oxygen before giving rise of free radicals which can damage of DNA, leading to improper cell DNA replication, causing cancers.
a.2. Cell communication
Researcher found that beta-carotene enhances the communication between cell can reduce the risk of cancer by making cells division more reliable.
a.3. Immune system
Beta-carotene promotes the immune system in identifying the foreign invasion such as virus and bacteria by increasing the quality of MHC2 protein in maintaining optimal function of white cells.
a.4. Polyunsaturated fat
Researchers found that beta-carotene also inhibits the oxidation of polyunsaturated fat and lipoprotein in the blood that reduce the risk of plaques build up onto the arterial walls, causing heart diseases and stroke.
a.5. There are more benefits of beta-carotene.

b. Alpha-carotene
Alpha-carotene, one of the most abundant carotenoids in the North American diet, is a form of carotene with a β-ring at one end and an ε-ring at the other. It is the second most common form of carotene which not only protects cells from the damaging effects of free radicals and enhances the immune system in fighting against bacteria and virus invasion, but also stimulates the communication between cells thus preventing irregular cell growth cause of cancers.

c. Beta-cryptoxanthin
Beta cryptoxanthin is an antioxidant, beside helping to prevent free radical damage to cells and DNA but also stimulates the repair of oxidative damage to DNA. it enhances the immune function infighting against inflammatory cause of polyarthritis, and irregular cell growth cause of cancer due to oxidation.

d. Lutein
Lutein is one of the most popular North American carotenoids. It is found in greens like kale and spinach as well as the yolk of eggs. Lutein is also found in the human eye. Getting enough lutein in your diet may help to fight off age related macular degeneration, an eye condition.
Researcher has shown that people who do not have enough lutein in their diet will not have enough lutein present in the muscular part of the eye. This is what likely leads to age related macular degeneration that can result in blindness.

e. Zeaxanthin
Zeaxanthin, a most common carotenoid alcohols found in nature, is one of the two primary xanthophyll carotenoids contained within the retina of the eye. Intake of foods providing zeaxanthin with lower incidence of age-related macular degeneration as a result of its function of reducing the risk oxidative stress.

f. Lycopene
Lycopene is a red carotene of the carotenoid group that can be found in tomatoes, watermelons, and grapefruits. This powerful antioxidant is believed to be a powerful fighter of prostate cancer. Lycopene has many anti-aging capabilities as well as one of the most powerful antioxidants in the carotenoid group.

3. Flavonoids
Flavonoids also known as Vitamin P and citrin are a yellow pigments having a structure similar to that of flavones occurred in varies plants. it has been in human history for over thousands of years and discovered by A. S. Szent-Gyorgi in 1930. As he used vitamin C and flavonoids to heal the breakage of capillaries, which caused swelling and obstruction of blood flow. Most plants have more than one group or type act as predominate.
Flavonoids process a property as antioxidants. it helps to neutralize many of reactive oxygen species (ROS), including singlet oxygen, hydroxyl and superoxide radicals.
Although nitric oxide is considered a free radical produced by immune system to destroy bacteria and cancerous cells, but when it is over produced, it causes the production peroxynitrite which may attack protein, lipid and DNA, Flavonoids inhibit NO production of peroxynitrite due to reduction of enzyme expression.
a. Quercetin
Quercetin is a plant-derived flavonoid found in fruits, vegetables, leaves and grains and studies show that quercetin may have anti-inflammatory and antioxidant properties as a antioxidant, quercetin scavenges free radicals, which damage cell membranes, cause mutation of cells with tampering DNA.

b. Rutin
Rutin is a citrus flavonoid glycoside found in buckwheat and glycoside of the flavonoid quercetin. It inhibits platelet aggregation, decreases the capillary permeability, makes blood thinner and improves circulation. As an antioxidant, it can reduce the cytotoxicity of oxidized LDL cholesterol caused by free radical that lowers the risk of heart diseases.

c. Catechin
Catechin is a natural phenol antioxidant plant and natural anti-bacterial substance. Study showed catechin as good free radical scavenging power inhibits ROS production, thus it can be useful to the development of alimentary strategies to prevent OTA-induced cytotoxicity in human.

d. Etc.

4. Uric acids
Uric acids may have a potential therapeutic role as an antioxidant becuase of its function of inducing oxidative stress, either through creating reactive oxygen species or inhibiting antioxidant systems.
High uric acid can cause arthritis, cardiovascular disease, diabetes, Metabolic syndrome, kidney stones, etc.

5. Thiols (R-SH)
Chemically, thiol, a organosulfur compound has strong odours resembling that of garlic. They are used as odourants to assist in the detection of natural gas. It presents in the amino acid cysseine which helps to the functioning of enzyme regulation, cell signaling, protein trafficking and control of gene expression. As a sulfide residue, thiol plays an important role in cell function of reversal oxidation by interacting with GSSG resulting in formation of intramucolar protein disulfide and GSG.

6. Coenzyme Q10
Coenzyme Q10 is discovered by Dr. Karl Folfers in 1957, beside promotes the chemical reaction, often by speeding it up or allowing it to proceed under less stringent conditions, it also enhances energy production by promoting the process of the production of ATP then serving as fuel for the cells and acts an antioxidant to prevent the generation of free radicals during this process.

7. Vitamin A, C, E. D.
a. Vitamin A
Vitamin A occurs in the form retinol and is best known for its function in maintaining the health of cell membrane, hair, skin, bone, teeth and eyes. It also plays an important role as an antioxidant as it scavenges free radicals in the lining of the mouth and lungs; prevents its depletion in fighting the increased free radicals activity by radiation; boosts immune system in controlling of free radicals; prevents oxidation of LDL and enhances the productions of insulin pancreas.

b. Vitamin C
Vitamin C beside plays an important role in formation and maintenance of body tissues, it as an antioxidant and water soluble vitamin, vitamin C can be easily carry in blood, operate in much of the part of body. By restoring vitamin E, it helps to fight against forming of free radicals. By enhancing the immune system, it promotes against the microbial and viral and irregular cell growth causes of infection and inflammation.
Vitamin C also is a scavenger in inhibiting pollution cause of oxidation.

c. Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols discovered by researchers Herbert Evans and Katherine Bishop. It beside is important in protecting muscle weakness, repair damage tissues, lower blood pressure and inducing blood clotting in healing wound, etc, it also is one of powerful antioxidant, by moving into the fatty medium to prevent lipid peroxidation, resulting in lessening the risk of chain reactions by curtailing them before they can starts.

d. Vitamin D
Reseacher found that vitamin D, a group of fat-soluble secosteroids is also a membrane antioxidant, with the ability to inhibit iron-dependent lipid peroxidation in liposomes compared to cholesterol.


8. Etc.
C.2. Omega 3 fatty acid
1. Antioxidative, anti-inflammatory, and anticarcinogenic activities
In the examination of the inhibition of inflammation as well as of cancer formation and growth in the lung and colon in animal models., using a tocopherol mixture that is rich in gamma-T (gamma-TmT, which contains 57%gamma-T), found that when given in the diet at 0.3%, gamma-TmT inhibited chemically induced lung tumorigenesis in the A/J mice as well as the growth of human lung cancer cell H1299 xenograft tumors. gamma-TmT also decreased the levels of 8-hydroxydeoxyguanosine, gamma-H2AX, and nitrotyrosine in tumors. More evident anti-inflammatory and cancer preventive activities of dietary gamma-TmT were demonstrated in mice treated with azoxymethane and dextran sulfate sodium. These results demonstrate the antioxidative, anti-inflammatory, and anticarcinogenic activities of tocopherols, according to "Inhibition of inflammation and carcinogenesis in the lung and colon by tocopherols" by Yang CS, Lu G, Ju J, Li GX.

2. Antioxidant and Antidiabetic Activities
In the determination of the antioxidant and antidiabetic activities of proximate composition, amino acids, fatty acids, tocopherols, sterols, glucosinolate and phenolic content in extracts, found that all examined extracts were prominently rich in phenolics and glucosinates, and they showed potent antidiabetic and antihemolytic activity. The present study could be helpful in developing medicinal preparations for the treatment of diabetes and related symptoms, according to "Compositional Studies: Antioxidant and Antidiabetic Activities of Capparis decidua (Forsk.) Edgew" by Zia-Ul-Haq M, Cavar S, Qayum M, Imran I, de Feo V.

3. The antioxidant and anti-inflammatory activities
In the investigation of the antioxidant and anti-inflammatory actions of tocopherols in mice and determination of whether the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is involved in these activities, indicated that the antioxidant and anti-inflammatory activities of γ-TmT in the colon are mostly due to the direct action of tocopherols in trapping reactive oxygen and nitrogen species, independent of the antioxidant enzymes and anti-inflammatory proteins that are regulated by Nrf2; however, Nrf2 knockout appears to affect the serum levels of tocopherol metabolites, according to "The antioxidant and anti-inflammatory activities of tocopherols are independent of Nrf2 in mice" by Li G, Lee MJ, Liu AB, Yang Z, Lin Y, Shih WJ, Yang CS.

4. Cognitive effects
In the examination of the relation of all plasma vitamin E forms and markers of vitamin E damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Within the AddNeuroMed-Project, plasma tocopherols, tocotrienols, α-tocopherylquinone, and 5-nitro-γ-tocopherol were assessed in 168 AD cases, 166 MCI, and 187 cognitively normal (CN) people, found that compared with cognitively normal subjects, AD and MCI had lower levels of total tocopherols, total tocotrienols, and total vitamin E. In multivariable-polytomous-logistic regression analysis, both MCI and AD cases had 85% lower odds to be in the highest tertile of total tocopherols and total vitamin E, and they were, respectively, 92% and 94% less likely to be in the highest tertile of total tocotrienols than the lowest tertile. Further, both disorders were associated with increased vitamin E damage. Low plasma tocopherols and tocotrienols levels are associated with increased odds of MCI and AD, according to "Tocopherols and tocotrienols plasma levels are associated with cognitive impairment" by Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, Baglioni M, Simmons A, Soininen H, Tsolaki M, Kloszewska I, Vellas B, Lovestone S, Mecocci P; AddNeuroMed Consortium.

5. Etc. 

C. 3. Phytochemicals
1. Allyl Sulfides(21)
a.  Immune system
According to the article of "GARLICTHE BOUNTIFUL BULB" by Carmia Borek, Ph.D. posted in Life extension magazine, the author indicated that human studies confirm immune stimulation by garlic. Subjects receiving aged garlic extract at 1800 mg a day for three weeks showed a 155.5% increase in natural killer immune cell activity that kills invaders and cancer cells. Other subjects receiving large amounts of fresh garlic of 35g a day, equivalent to 10 cloves, showed an increase of 139.9%. In six weeks, patients with AIDS receiving aged garlic extract showed an enhancement of natural killer cells from a seriously low level to a normal level.

b. Neurological disease
According to the study of " Antioxidant Health Effects of Aged Garlic Extract" by Carmia Borek, posted in (Journal of Nutrition. 2001;131:1010S-1015S.)© 2001 The American Society for Nutritional Sciences, researcher indicated that the studies suggest that AGE may have antiaging effects and help in preventing age-related deterioration of brain function that are linked to dementia and Alzheimer’s disease.

c. Antioxidant against oxidation
According to the study of " Antioxidant Health Effects of Aged Garlic Extract" by Carmia Borek, posted in (Journal of Nutrition. 2001;131:1010S-1015S.)© 2001 The American Society for Nutritional Sciences, researcher found that AGE contains a wide range of antioxidants that can act in synergistic or additive fashion and protect cells against oxidative damage, thus helping to lower the risk of heart disease, stroke, cancer and Alzheimer’s disease and protect against toxic, tissue-damaging effects of ROS-producing radiation, including UV light, drugs used in therapy and chemicals in the environment and industry.

d. Detoxification
Looking for a natural detox? Allyl Sulfides declare war against toxins. They do this by stimulating the enzymes that eliminate toxins from the body. These enzymes are located in the digestive system. They are part of the normal digestive process. The Allyl Sulfides in onions and garlic simply encourage them to work harder and faster to eliminate toxins.

2. Allyl isothiocyanate(22)
a.  Antimicrobial effects
In the investigation of the antimicrobial effect of a chitosan coating+allyl isothiocyanate (AIT) and nisin against Salmonella on whole fresh cantaloupes, showed that The same coating treatment completely inactivated mold and yeast on cantaloupe at day 1 and no regrowth occurred even up to 14days of storage. Scanning electron microscopy revealed that cell membrane damage and leakage of intercellular components occurred as a result of the chitosan-AIT coating treatments. No visual changes in overall appearance and color of cantaloupe rind and flesh due to coating treatments were observed. These results indicate that the application of an antimicrobial coating may be an effective method for decontamination of cantaloupes, according to "Inactivation of Salmonella on whole cantaloupe by application of an antimicrobial coating containing chitosan and allyl isothiocyanate" by Chen W, Jin TZ, Gurtler JB, Geveke DJ, Fan X.

b.  Anti-inflammatory effects
In the evaluation of the underlying mechanisms of the potential anti-inflammatory properties of allyl-isothiocyanate (AITC) were analysed in vitro and in vivo, showed that 1. AITC was slightly less potent than sulforaphane (used as a positive control) in down-regulating inflammation in LPS stimulated macrophages. A significant increase in nuclear Nrf2 and heme oxygenase 1 gene expression and only a moderate down-regulation of interleukin 1β and microRNA-155 levels due to AITC was found in mouse liver. Present data suggest that AITC exhibits potent anti-inflammatory activity in cultured macrophages in vitro but has only relatively little anti-inflammatory activity in mice in vivo, according to "Anti-inflammatory potential of allyl-isothiocyanate-role of Nrf2, NFκB and microRNA-155" by Wagner AE, Boesch-Saadatmandi C, Dose J, Schultheiss G, Rimbach G.

c. White Blood Cells (WBCs)
In the investigation of the effects of AITC (dose=20 mg/kg body weight/day for 10 days, subcutaneous: s.c.) on the number of WBCs (total WBCs, lymphocytes, monocyte, neutrophil, basophil and eosinophil) and plasma corticosterone concentrations in adult male rats, showed that administration of AITC decreased significantly the number of total WBCs on days 1-4 post s.c. injection by 25-27%. AITC also decreased the number of lymphocytes on days 1-10 by 21-36% and monocyte on days 1-8 by 28-78%. However, administration of AITC increased the number of neutrophil on days 8-10 by 61-112%. AITC did not change the number of eosinophil and basophil. Plasma corticosterone concentrations during the experimental period were 4.7-8.4 times significantly higher in the AITC group than in the control group, indicating that AITC induced stress-responses, according to "Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats" by Imaizumi K, Sato S, Sakakibara Y, Mori S, Ohkuma M, Kawashima Y, Ban T, Sasaki H, Tachiyashiki K.

3. Etc.
 
Treatments and management
A. In conventional medicine perspective
 Management of central nervous system (CNS) involvement still remains one of the most challenging problems in systemic lupus erythematosus (SLE). In the assessment of the diseases, some researchers suggested that the choice of treatment depends on the most probable underlying pathogenic mechanism and the severity of the presenting neuropsychiatric symptoms. Patients with mild manifestations may need symptomatic treatment only, whereas more severe acute nonthrombotic CNS manifestations may require pulse intravenous cyclophosphamide. Plasmapheresis may also be added in patients with more severe illness refractory to conventional treatment. Recently, the use of intrathecal methotrexate and dexamethasone has been reported in a small series of patients, with a good outcome in patients with severe CNS manifestations. Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid syndrome (APS). This article reviews the clinical approach to therapy in patients with CNS lupus(15)
Other suggested that the therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their usefulness in the treatment of neuropsychiatric SLE(16) 
1. Symptomatic therapy
1.1. Symptomatic therapy is defined as a medical therapy used to treat the symptoms of the disease but not its causes, such as Anti-inflammatory, Analgesic, Antitussives agents, etc.

b. Side effects are not limit to
b.1. Anti-Inflammatory agent (hypertension, skin rash and itching, gastrointestinal discomforts, ulcers and bleeding, kidney damage, etc.
b.2.  Analgesics (long-term use of pain relievers can be addictive, stomach irritation, Over doses (2000 mg/day or more) can cause liver damage, etc.
b.3. Antitussives agents (Nausea, vomitin, skin rash and itching, welling,  dizziness, etc.

2. Intravenous cyclophosphamide, methotrexate or dexamethasone or immunoglobulin
a. Depending to the severity of the diseases, medical condition, weight, response to therapy cyclophosphamide or methotrexate or dexamethasone or immunoglobulin is injection into a vein by your doctor or a healthcare professional.

b. Side effects sre not limit to
b.1. Cyclophosphamide (Nausea, vomiting, loss of appetite, stomach ache, diarrhea, s, temporary hair loss,  unusual tiredness or weakness, joint pain, easy bruising/bleeding, etc.)
b.2. Methotrexate (Dizziness, general body discomfort, headache, loss of appetite, mild sore throat, mild stomach pain, nausea, vomiting, tiredness, etc.)
b.3. Dexamethasone (Difficulty sleeping, feeling of a whirling motion, increased appetite and sweating, indigestion; mood swing, nervousness, etc.)
b.4. Immunoglobulin(headache, dermatitis, chills, migraine, dizziness, fever, nausea, vomiting, fatigue , itching, increased Blood Pressure etc.)

3. Immunosuppressive Therapy
a. Immunosuppressive Therapy is defined as the treatment to suppress the immune response to antigen(s), on most cases it is used in conditions such as organ transplantation, autoimmune disease, allergy, etc.

b. Side effects are not limit to
b.1. Fever
b.2. High blood pressure
b.3. Kidney function.
b.4. Researchers found that Remissions were cyclosporine dependent in 26% of the patients responding to a regimen that included cyclosporine. Clonal or malignant diseases developed in 25% of the patients.(17)
b.5. Etc.

4.  Anticoagulant therapy
a. Anticoagulants is also well as blood thinners, used to slow the rate of blood clots of diseases such as thrombosis to atrial fibrillation.
b. Side effects are not limit to
b.1. Itching,
b.2. Rashes
b.3. Easy bruising,
b.4. Increased the risk of bleeding from injuries
b.5. Purplish spots on the skin
b.6. Etc.

5. Etc. 

B. In herbal medicine perspective
Herbs used to treat and manage lupus are associated to anti inflammation and enhanced immune system as the diseases are characterized as lupus is mainly thought of as an autoimmune disorder also considered a rheumatic condition
B.1. Immune system enhancing herbs
1. Andrographis 
Andrographis paniculata (Burma) Wall. ex Ness (AP) beside have been used to treat upper respiratory tract infection (URI) as well as acute diarrhea, but its leaves also have exerted the activity of anti-bacteria against infection, according to the study of "Undetectable anti-bacterial activity of Andrographis paniculata (Burma) wall. ex ness" by Leelarasamee A, Trakulsomboon S, Sittisomwong N.(43)

2. Astragalus
Astragalus polysaccharides (APS) isolated from astragalus enhances the immune system by enhancing and regulating the function of T cells, by suppressing the CD4(+)CD25(+)Treg activity, at least in part, via binding TLR4 on Tregs and trigger a shift of Th2 to Th1, according to the study of "Astragalus polysaccharides attenuate postburn sepsis via inhibiting negative immunoregulation of CD4+ CD25(high) T cells" by Liu QY, Yao YM, Yu Y, Dong N, Sheng ZY., posted in PubMed(44)

3. Echinacea 
In the observation of ethanolic extract of fresh Echinacea purpurea and the changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration found that Echinaforce regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress, according to the study of "Effects of Echinaforce® treatment on ex vivo-stimulated blood cells" by Ritchie MR, Gertsch J, Klein P, Schoop R.(46)

4. Goldenseal 
In the investigation of new potential sources of antimicrobial agents to Neisseria gonorrhoeae (Ng) resistance found that Extracts of Arctostaphylos uva ursi (kinnikinnick or bearberry), Hydrastis canadensis (goldenseal), Prunus serotina (black cherry), and Rhodiola rosea (roseroot) inhibited the growth of all Ng isolates with minimum inhibitory concentrations of 32 μg/mL, 4 to 32 μg/mL, 16 to >32 μg/mL, and 32 to 64 μg/mL, respectively. Extracts of Acorus americanus (sweet flag), Berberis vulgaris (barberry), Cimicifuga racemosa (black cohosh), Equisetum arvense (field horsetail), Gaultheria procumbens (wintergreen), Ledum groenlandicum (Labrador tea), Ledum palustre (marsh Labrador tea), Oenothera biennis (common evening primrose), Sambucus nigra (elderberry), and Zanthoxylum americanum (prickly ash) had weak or no antimicrobial activity against the Ng isolates with minimum inhibitory concentrations ≥256 μg/mL, according to "Extracts of Canadian first nations medicinal plants, used as natural products, inhibit neisseria gonorrhoeae isolates with different antibiotic resistance profiles" by Cybulska P, Thakur SD, Foster BC, Scott IM, Leduc RI, Arnason JT, Dillon JA.(47)

5. Cat's Claw 
a. Oral extract of Cat's claw has demonstrated the activity of protection against indomethacin-induced gastritis, and prevention of TNFalpha mRNA expression and apoptosis, according to the study of `Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content`by Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ.(48)

b. Extract of U. tomentosa ingested daily for 15 days by a smoker has decreased the mutagenicity induced in S. typhimurium TA98 and TA100 by the subject's urine, according to the study of `Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts`by Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L, Stivala LA.(49)

6. Etc.



B.2. Anti inflammatory herbs
1. Aloe Vera
Aloe Vera also is popular used in treating infection and inflamation as a result of its antioxidant property. according to the study of " In Vitro Antimicrobial and Antioxidant Activities of Anthrone and Chromone from the Latex of Aloe harlana Reynolds" by Asamenew G, Bisrat D, Mazumder A, Asres K., (50)

2. Ginger
In the classification of the effect of ginger extract on the expression of NFκB and TNF-α in liver cancer-induced rats found that ginger extract significantly reduced the elevated expression of NFκB and TNF-α in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFκB through the suppression of the pro-inflammatory TNF-α, according to "Ginger Extract (Zingiber Officinale) has Anti-Cancer and Anti-Inflammatory Effects on Ethionine-Induced Hepatoma Rats" by Shafina Hanim Mohd Habib,I Suzana Makpol, Noor Aini Abdul Hamid, Srijit Das, Wan Zurinah Wan Ngah, and Yasmin Anum Mohd Yusof (51)

3. Saw Palmetto
In the Investigate the antiinflammatory activity of Serenoa repens (SeR), LY, and) on proinflammatory phenotype in rat peritoneal macrophages (Ms) found that the Ly-Se-SeR association caused a greater inhibitory effect on the expression of COX-2, 5-LOX, and iNOS. The Ly-Se-SeR association showed a higher efficacy in reducing the loss of IκB-α, the increased NF-κB binding activity, the enhanced mRNA levels of TNF-α, the elevated MDA, and nitrite content, according to "Effect of Serenoa repens, lycopene, and selenium on proinflammatory phenotype activation: an in vitro and in vivo comparison study" by Bonvissuto G, Minutoli L, Morgia G, Bitto A, Polito F, Irrera N, Marini H, Squadrito F, Altavilla D.(52)

4. Astragalus
Astragalus has exerted an anti-inflammatory effect as a result of inactivation the p38 and Erk1/2 and inhibition NFkappaB-mediated transcription, according to the study of "Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk" by Ryu M, Kim EH, Chun M, Kang S, Shim B, Yu YB, Jeong G, Lee JS., posted in PubMed(45)

5. Green tea
In the investigation of l-Theanine is a unique amino acid in green tea effects on ethanol-induced liver injury of the study of "l-Theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes" by Li G, Ye Y, Kang J, Yao X, Zhang Y, Jiang W, Gao M, Dai Y, Xin Y, Wang Q, Yin Z, Luo L[5a], researchers found that l-theanine significantly inhibited ethanol-induced reduction of mouse antioxidant capability which included the activities of SOD, CAT and GR, and level of GSH. These results indicated that l-theanine prevented ethanol-induced liver injury through enhancing hepatocyte antioxidant abilities(53)

6.  Etc.

C. In Chinese medicine perspective 
Depending to the  symptoms and differentiation together with the physical exam and appearance, etc. Systemic lupus erythematosus (SLE) can be classified as(54)
C. 1. Toxin heat invasion
1. Symptoms
Acute stage - red eruptions with a high fever, irritability
2. Formula used to treat used for all types of bleeding due to Heat and Blood Stasis. (Do not use for bleeding due to Spleen deficiency)
2.1. Xi Jiao Di Huang Tang
a. Xi Jiao (cornu rhinoceri) 3g
b. Sheng Di Huang (radix rehmanniae glutinosae) 24g
c. Shao Yao (radix paeoniae) 9g
d. Mu Dan Pi (cortex moutan radicis) 6g

2.2. Wu Wei Xiao Du Yin
a. Jin Yin Hua (honeysuckle flower) 9g
b. Pu Gong Ying (dandelion) 3.6g
c. Zi Hua Di Ding (viole) 3.6g
d. Ye Ju Hua (wild chrysanthemum flower) 3.6
e. Zi Bei Tian Kui (Begonia) 3.6g


C.2. Internal Heat due to Yin-Deficiency
1. Symptoms
Slight fever, fatigue, dry mouth, flushed face, red cheeks, nocturnal emissions, chronic sore throat, frequent urination of dark

2. Formula
Zhi Bai Di Huang Tang used to treat insufficient liver and kidney yin plus heat signs.  
2.1. Zhi Bai Di Huang Tang
a, Shu Di (Rehmannia prepared root)  (21.7%)
b. Zhi Mu (Anemarrhena root)(16.2%)
c. Huang Bai (Phellodendron bark)(16.2%) 
d. Shan Zhu Yu (Cornus fruit)(10.8%)
e. Shan Yao (Dioscoria root)(10.8%) 
f. Fu Ling (Poria cocos fungus) (8.1%) 
g. Mu Dan Pi (Moutan bark)(8.1%)
h. Ze Xie (Alisma rhizome) (8.1%)

C.3. Spleen-Yang and Kidney-Yang Deficiency  
Fatigue, edema, puffy, brittle hair, menstrual disorder, digestive disorder 2. Formula
Ling Gui Zhu Gan Tang used to transforms Phlegm-fluids, strengthen Spleen, clear Damp
a. Fu Ling (sclerotium poriae cocos) 12g
b. Gui Zhi (ramulus cinnamomi cassiae) 9g
c. Bai Zhu (rhizoma atracylodis macrocephalae) 6g
d. Zhi Gan Cao (honey fried radix glycyrrhizae uralensis) 6g

+ Shen Ling Bai Zhu San used to nourish Spleen, enhance the digestive function and removes Dampness
e. Ren Shen (Radix Ginseng)
f. Fu Ling (Sclerotium Poriae Cocos)
g. Bai Zhu (Rhizoma Atractylodis Macrocephalae)
h. Shan Yao (Rhizoma Dioscoreae Opposita)
i. Lian Zi (Semen Nelumbinis Nuciferae)
j. Bai Bian Dou (Semen Dolichoris Lablab)
k. Yi Yi Ren (Semen Coicis Lachryma-Jobi)
l. Sha Ren (Fructus Amomi)
m. Jie Geng (Radix Platycodi Grandiflori)
n. Gan Cao (Radix Glycyrrhizae Uralensis)


Author note: the article is for information and education only, please consult with your doctor or related field specialist before applying.

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Hemicrania continua (HC)

Hemicrania continua (HC) is a chronic and persistent unilateral headache and considered as one of primary headache disorders, according to International Headache Society's International Classification(1), affecting 4 to 5% of the general population.

I. Symptoms
In the report of two patients with side-shifting HC with aura, showed that these patients' symptoms are [1]unilateral headaches, [2]visual aura, [3]autonomic features, [4]throbbing pain, [5]nausea and [6]photo/phonophobia(2), runny nose[7], tearing and redness of the eyes[8], sweating[9], drooping eyelids[10] nausea, vomiting[11] and sensitivity to light[12](3). Other symptoms include trigeminal-autonomic cephalalgias[13] and migraine[14] (4)

II. Causes and Risk factors
Some researchers suggested that that secondary or symptomatic HC is associated with another neurological or non-neurological disease. In the a report of three patients with secondary HC and the also review the literature to identify the clinical predictors of an underlying disease entity. Intracranial structural lesion, head and neck vessel pathology, and carcinoma lung should be suspected in every patient. The factors that may suggest a secondary pathology are: elderly age, male sex, smoking habit, constitutional symptoms, symptoms related to respiratory system, frequent and short-lived exacerbation, nocturnal exacerbation, HC evolving from remitting form, recent neck and/or head trauma, miosis, elevated ESR, and fading effect of indomethacin. We recommend MRI brain in all the patients presenting with HC or HC like headache. Angiography and CT chest are two other investigations that may be supplemented in patients with high risk for head/neck vessel pathology and carcinoma lung.(5).
Other researchers suggested that patient who suffered from cluster headache may evolving into ipsilateral HC, as they do not tolerate a long-term indomethacin therapy(6). Other found that HC is a life long condition, and skipping of a single dose of indomethacin usually leads to reappearance of headache(7)

Misdiagnosis 
Diagnosis is difficult, in a report of a woman in her fifties, with a long history of side-locked unilateral headache, was hospitalized for left-sided side-locked paroxysmal headache (attacks with 10-20 min duration), indicated that a retrospective review of her medical history showed 15 years of unsuccessfully treated unilateral headache, until she responded completely to rofecoxib. Ipsilateral cranial autonomic symptoms also supported the diagnosis of hemicrania continua, although these symptoms presented before indomethacin was tried. Diagnostic delay and misdiagnoses of unilateral headaches, as illustrated by this case, shows the clinical controversies and difficulties in diagnosing and treating this condition.(8).
Others suggested that Misdiagnosis of HC is probably common in general neurology settings and other clinical specialties. Dr. Peres MF and the team at the UNIFESP (Universidade Federal de São Paulo), São Paulo, said "the gap between the correct and misdiagnosis of this disorder. HC was once thought to be a rare headache disorder, but is, in fact, an under-recognized headache syndrome. HC can be of continuous or remitting form. Variants such as HC with aura have been described and secondary cases may occur"(9)

Diagnosis 
many researchers believe the diagnosis of Hemicrania continua (HC) consists of the symptoms and signs of  [1]unilaterality without side shift; [2]absolute indomethacin effect; [3] and long-lasting repetitive attacks of varying duration[4], eventually with a chronic pattern, the pain being mild to severe[5](10).Other suggested clinically, HC is considered a syndrome with two pivotal characteristics: (i) strictly unilateral (moderate, fluctuating, relatively long-lasting) headache; and (ii) absolute response to indomethacin. HC is further characterized by some ancillary, but mostly "negative", features such as: (iii) relative paucity of accompaniments; and (iv) lack of precipitating factors.(11)

Treatments
1. Indomethacin
Many researchers believe that Hemicrania continua is one of the indomethacin-responsive headache syndromes, patients may require daily indomethacin for years. The risks of long-term indomethacin include gastrointestinal and renal dysfunction, but according to the study from the team and Dr. JA Pareja found that Six (23%) patients showed adverse events, mostly gastrointestinal and relieved with ranitidine. No major side-effects were observed. These results indicate that prolonged indomethacin treatment of HC or CPH has a good safety and tolerability profile with a reduction of up to 60% in the initial dose.

2.  Melatonin
Other suggested that Melatonin is a pineal hormone with a chemical structure very similar to indomethacin as melatonin was shown to be effective for primary stabbing headache, another indomethacin-responsive syndrome.(12)

3.  Other studies point out possible alternatives: Gabapentin, topiramate, cyclooxygenase-2 inhibitors, piroxicam, beta-cyclodextrin, amitriptyline, melatonin. Other drugs were described in different reports as efficient, but most of them were considered inefficient in other HC cases.(13) and a report of two cases of HC responsive to topiramate and review the available alternatives for the patients of HC. The side effects of indomethacin in the various headache disorders and other painful conditions, and may need for trial of other drugs for the patients of HC.(14)

4. Etc.

Side effects
Side effects of indomethacin are not limit to
1. Indomethacin HC is a life long condition, and
2. Skipping of a single dose of indomethacin usually leads to reappearance of headache.(14)
3. risk for serious stomach/intestinal bleeding.
4. Others not common side effects include chest pain, shortness of breath, weakness on one side of the body, sudden vision changes, slurred speech.
5. Gastrointestinal and renal dysfunction.(15)
6. Etc.

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Sources
(1) http://www.ihs-headache.org/upload/ct_clas/ihc_II_main_no_print.pdf
(2) http://www.ncbi.nlm.nih.gov/pubmed/16886926
(3) http://headaches.about.com/lw/Health-Medicine/Conditions-and-diseases/All-About-Hemicrania-Continua-Headaches.htm
(4) http://www.ncbi.nlm.nih.gov/pubmed/22440373
(5) http://www.ncbi.nlm.nih.gov/pubmed/19215945
(6) http://www.ncbi.nlm.nih.gov/pubmed/19006550
(7) http://www.ncbi.nlm.nih.gov/pubmed/19041987
(8) http://www.ncbi.nlm.nih.gov/pubmed/21494306
(9) http://www.ncbi.nlm.nih.gov/pubmed/19769451
(10) http://www.ncbi.nlm.nih.gov/pubmed/11903280
(11) http://www.ncbi.nlm.nih.gov/pubmed/11843864
(12) http://www.ncbi.nlm.nih.gov/pubmed/16866728 
(13) http://www.ncbi.nlm.nih.gov/pubmed/22440373
(14) http://www.ncbi.nlm.nih.gov/pubmed/19041987
(15) http://www.ncbi.nlm.nih.gov/pubmed/16866728

Reversible cerebral vasoconstriction syndrome - Headache/Stroke

I. Stroke is a result of a blockage in the blood vessels (ischemic stroke) or bleeding (hemorrhagic stroke) of that associated ischemic stroke, transient ischemic attack, or non-traumatic intracranial hemorrhage, including intracerebral and subarachnoid hemorrhage, etc. according to "Headache attributed to stroke, TIA, intracerebral haemorrhage, or vascular malformation" by Carolei A, Sacco S.(1)

II. A headache or cephalalgia is defined as a condition of pain in the region around the head or neck. Normally, it is a symptom of a number of different effects of certain diseases or the head and neck themselves. High headache impact was proven to be associated with worse academic performance.

III. Reversible cerebral vasoconstriction syndrome (RCVS)
Reversible cerebral vasoconstriction syndrome, sometimes called Call-Fleming syndrome is defined as a condition of disease of the arteries of which the brain develops a blood vessels spasm that leads to multifocal arterial constriction and dilation, causing the sudden onset of a severe headache (2)
1. Does stroke causes headache?
A sudden severe headache or recurrent of thunderclap headache may be a beginning of a stroke as a result of a hemorrhagic stroke.
 
2. Does headache causes stroke?
Cerebral vasoconstriction due to severe headache may cause completely stop blood flow to a portion of the brain, causing stroke if the blood vessel can not relax fast for blood to flow again(2)

II. Symptoms
1. Sudden-onset thunderclap headache or recurrent severe headache
2. Dysarthria
Dysarthria is defined as a condition of motor speech disorder resulting from neurological injury of the motor component of the motor-speech system due to the can spontaneously constriction of and relax back and forth over a period of time of cerebral arteries.
3. Nausea, Vomiting, Photophobia, Confusion and Blurred vision(3)
4. Unsteady movement of the limbs
5. Overactive or overresponsive reflexes
As a result of upper motor neuron damage causes of focal neurological symptoms.
6. Etc.


V. Causes and risk factors
Some researchers suggested reversible cerebral vasoconstriction syndrome (RCVS) may be a results from a transient disturbance of the circle of arteries that supply blood to the brain of which leads to its constriction.
1. Antidepressants
Antidepressants used to treat depression, anxiety disorders, and some personality disorders may increase risk of diffuse cerebral vasoconstriction(5)

2. Nasal decongestants
In the investigation conducted by Lariboisière Hospital of clinical, neuroimaging and outcome data of 67 consecutive patients prospectively diagnosed over 3 years in our institution with an angiographically confirmed RCVS, 43 females and 24 males with a mean age of 42 years (19-70). RCVS was spontaneous in 37% of patients and secondary in the 63% others, to postpartum in 5 and to exposure to various vasoactive substances in 37, mainly cannabis, selective serotonin-recapture inhibitors and nasal decongestants(6)

3. Eletriptan  
A pediatric case of reversible cerebral vasoconstriction syndrome with cortical subarachnoid hemorrhage, suggested that Eletriptan might cause vasoconstriction of cerebral arteries. Although most patients with RCVS are adults and pediatric cases are rare, RCVS should be considered in a child complaining of severe headache(7)

4. Vasoconstrictive drug exposure and migraine
In the study of clinical, laboratory, and imaging features of patients with reversible cerebral vasoconstriction syndromes evaluated at 2 academic centers, compare subgroups, conducted by

6. Evoked by pregnancy(4)

7. Exposure to vasoactive substances such as angiotensin II, epinephrine, norepinephrine, vasopressin can lead to constrictor dilate of blood vessels)(4)

8. Etc.

VI. Diagnosis
A. Misdiagnosis
Reversible cerebral vasoconstriction syndrome (RCVS) constitutes an under-recognised but clinically important diagnosis, because it can be complicated by a cerebrovascular accident. The syndrome is often misdiagnosed as it resembles. Misdiagnosis of Reversible Cerebral Vasoconstriction Syndromes as primary cerebral vasculitis and aneurysmal subarachnoid hemorrhage is common because of overlapping clinical and angiographic features, researchers at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and Cleveland Clinic Foundation, said, as reversible cerebral vasoconstriction syndromes (RCVS) comprise a group of diverse conditions, all characterized by reversible multifocal narrowing of the cerebral arteries heralded by sudden (thunderclap), severe headaches with or without associated neurologic deficits(11). Other study reported demonstration of two female patients presented with severe headache with subsequent angiographic findings of ‘bead and string’ appearances of the cerebral arteries at Circle of Willis, which resolved spontaneously within 3 months. Diagnosis of reversible cerebral vasoconstriction syndrome was made. The clinical and imaging characteristics in different modalities are discussed(10)

1. Primary Angiitis of the Central Nervous System
Primary angiitis of the central nervous system is defined as an idiopathic disorder characterized by vasculitis within the dural confines. Headache and encephalopathy are the most frequent initial symptoms. Stroke or focal symptoms develop in less than 20% of patients at the onset of disease and are uncommon in the absence of headache or encephalopathy. Symptoms or signs of vasculitis outside of the central nervous system are rare; serologic markers of inflammation are typically normal(16). A Medline search was performed to identify all case reports since 1966 describing RCVS and PACNS that provide sufficient clinical detail to permit diagnostic classification according to published criteria. RCVS included case studies in which there was angiographic or transcranial Doppler ultrasound evidence of near-to-complete resolution of cerebral vasoconstriction in the absence of a well-recognized secondary cause. PACNS included reports of histologically confirmed PACNS either through biopsy or necropsy(17)

2. Post-partum cervicocephalic artery dissection (pp-CAD)
In a report of a 41-year-old right-handed African-American woman who developed the syndrome of pp-CAD (headaches, trace subarachnoid hemorrhage and diffuse cerebral arteriopathy on angiogram), researchers at the Northwestern University, hypothesized whether transient arterial wall abnormalities, postpartum hormonal changes or subtle connective tissue aberrations play a similar role in the pathogenesis of these two associated Post-partum cervicocephalic artery dissection (pp-CAD) and Reversible cerebral segmental vasoconstriction (RCSV)(16)

3. Subarachnoid Haemorrhage
Subarachnoid hemorrhage is defined as a bleeding in the subarachnoid space area between the brain and the thin tissues that cover the brain, causing certain similar symptoms to those of Reversible cerebral vasoconstriction syndrome. In the report of the case of a 51-year-old woman who presented to hospital following a thunderclap headache, initially thought to be secondary to a subarachnoid haemorrhage (SAH). A tiny anterior choroidal artery aneurysm was demonstrated on cerebral angiogram. At surgical clipping, no evidence of haemorrhage was observed. Post-operatively, the patient developed delayed right-sided hemiparesis, managed with aggressive hypertensive treatment, and later, with onset of septicaemia, central visual loss. Computed tomography (CT) brain scans demonstrated oedematous changes within the parieto-occipital regions bilaterally and later areas of infarction. The initial diagnosis of SAH was revised to reversible cerebral vasoconstriction syndrome (RCVS), which gave rise to Posterior reversible encephalopathy syndrome (PRES)(18). Another report on a pediatric case of RCVS with cortical subarachnoid hemorrhage (SAH). A 12-year-old boy developed acute, severe headache with paralysis of lower extremities causing gait disturbance after administration of eletriptan. Brain magnetic resonance angiography (MRA) revealed multifocal narrowing of the cerebral arteries, whereas magnetic resonance imaging (MRI) demonstrated sulcal hyperintensity on fluid-attenuated inversion recovery, consistent with cortical SAH. The patient's clinical symptoms resolved spontaneously after a few days and the MRI and MRA findings disappeared 3months later, suggesting a diagnosis of RCVS. Eletriptan might cause vasoconstriction of cerebral arteries. Although most patients with RCVS are adults and pediatric cases are rare, RCVS should be considered in a child complaining of severe headache.(19)

4. Orgasmic headache
Orgasmic headache (OH) is a condition of an "explosive" headache that occurs at orgasm. In a report of 34-year-old woman who presented with isolated and recurrent TCH at orgasm, which fulfilled the diagnosis of OH. However, she was post-partum and had recent exposure to ecstasy, making her symptoms highly suggestive of RCVS. Brain magnetic resonance angiography showed segmental vasoconstriction(15)

5. Etc.

B. Diagnosis
1. Catheter angiogram 
Catheter angiogram, is the use of a thin plastic tube, called a catheter, is inserted into a large artery and threaded through the circulatory system to the carotid artery, through a small incision in the skin, together with X-rays and a contrast dye in visualizing the blood vessels of the brain. Then a series of radiographs is taken as the contrast agent spreads through the brain's arterial system, then a second series as it reaches the venous system.

2. CT scan
CT scan can dive your doctor a three-dimensional view of your blood vessels of the brain to look for masses and other abnormalities that cause Reversible cerebral vasoconstriction syndrome

3.  Magnetic resonance imaging (MRI)
By using radio waves and magnetic fields to take pictures, MRI scan provides very high quality of a cross-sectional slice and lengthwise slices of the brain and thus providing the better and detail image of location of tumor and the surrounding structures. It is one of most likely early test ordered by a doctor to diagnose tumors, strokes, aneurysms, neurological diseases and other brain abnormalities and the blood vessels around the brain.

4. Computed tomography angiography (CTA)
CTA is a test to create detailed images of the blood vessels of the brain to look for neurological diseases and any abnormality with the use of the combination of the technology of a conventional CT scan with that of traditional angiography.

5. Cerebral magnetic resonance angiography (MRA)
Magnetic resonance angiography (MRA) is an accurate non-invasive tool for imaging the cerebral vessels. It provides morphologic information about the cerebral vessels relying on blood flow as the physical basis for generating contrast between stationary tissues and moving spins. 'Selective' MRA gives functional information about the cerebrovascular system such as flow direction, origin of flow, and presence or absence of collaterals. Arteries and veins can be imaged selectively due to their usually opposite flow directions. Although at a relatively early stage of development, MRA has already become a widely used tool for the study of the cerebrovascular system(12)
In the study of One hundred five (79%) of all 133 aneurysms detected with MRA by a neuroradiologist, 100 (75%) detected by an experienced neurosurgeon, 84 (63%) detected by a general radiologist, and 80 (60%) detected by a resident neuroradiologist, conducted by Nagatomi Neurosurgical Hospital, found that although MRA is useful in the diagnosis of cerebral aneurysms, sufficient experience and careful attention are necessary for accurate diagnosis of aneurysms located at the internal carotid and anterior cerebral arteries(13)

6. Etc.

VIII. Treatments
1. Calcium channel inhibitors (nimodipine, nifedipine or verapamil)
a. In the observation of a 63-year-old female with developed visual field impairment and a right-sided hemiparesis. Brain MRI revealed bilateral posterior and left parietal ischaemic strokes and  Cerebral catheter angiography showed segmental arterial vasoconstriction, after 11 days onset of headache, a vasodilative therapy with calcium channel inhibitors was started and serial transcranial Doppler ultrasonography demonstrated resolution of cerebral arterial vasoconstriction(14)
b. Side effects are not limit to
b.1. Constipation
b.2. Nausea,
b.3 Headache
b.4. Rash,
b.5. Edema
b.6. Low blood pressure
b.7. Drowsiness, and dizziness
b.8. Etc.

2. Corticosteroids
a. Corticosteroids (commonly called steroids) are synthetic medicine closely resemble cortisol, a hormone produced adrenal glands produce naturally. In the report of a severe case of a 53-year-old woman with RCVS having an unruptured cerebral aneurysm and presenting as cortical subarachnoid hemorrhage, reversible posterior leukoencephalopathy syndrome, and cerebral infarction, by Juntendo University Shizuoka Hospital showed that the patient was successfully treated with corticosteroids and a calcium channel blocker and the aneurysm was clipped. Her various complications are due to the responsible vasoconstriction that started distally and progressed towards proximal arteries. This case demonstrates the spectrum of presentations of RCVS, a clinically complicated condition(20)

b. Side effects are not limit to
b.1. Bones thinning,
b.2. Avascular necrosis of bones
b.3. Swelling of the face
b.4. The medicine can inhibit natural hormones
b.5. It may cause liver damage
b.6. It may lower HDL cholesterol, and raise LDL cholesterol
b.7. Etc.

3. Intravenous magnesium sulfate
a. Magnesium sulfateis is a chemical compound with the formula MgSO4. In the report of four postpartum women aged 15 to 33 years developed acute neurologic deficits 1 to 8 days after uncomplicated deliveries. One had a history of migraine headaches and 2 had histories of spontaneous abortion. Two of the patients had uneventful pregnancies and 2 had preeclampsia, 1 of whom had acute hepatic failure, conducted by Jennifer E and the team showed that aggressive treatment was attempted with most patients including intravenous magnesium sulfate, corticosteroids, calcium channel blockers, balloon angioplasty, vasopressors, and osmotic agents. Two patients underwent serial angiography, with results showing severe, recurrent proximal vasoconstriction involving all major intracranial vessels.

b. Side Effects are not limit to
b.1. It may cause severe allergic reactions, including rash; hives; itching; difficulty breathing; tightness in the chest swelling of the mouth, face, lips, or tongue.
b.2. Dizziness
 b.3. Flushing;
b.4. Irregular heartbeat
b.5. Sweating
b.6. Etc.

4. Etc.
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/20816453
(2) http://www.ncbi.nlm.nih.gov/pubmed/19220301 
(3) http://www.ncbi.nlm.nih.gov/pubmed/20936928
(4) http://www.ncbi.nlm.nih.gov/pubmed/21179608
(5) http://www.ncbi.nlm.nih.gov/pubmed/16832100
(6) http://www.ncbi.nlm.nih.gov/pubmed/18025032
(7) http://www.sciencedirect.com/science/article/pii/S038776041200006X
(8) http://www.medscape.org/viewarticle/748234_3
(9) http://www.ncbi.nlm.nih.gov/pubmed/22000400
(10) http://www.hkcr.org/publ/Journal/vol13no3/full/149-53%20Imaging.pdf
(11) http://www.ncbi.nlm.nih.gov/pubmed?term=Narrative%20Review%3A%20Reversible%20Cerebral%20Vasoconstriction%20Syndromes
(12) http://www.biomedsearch.com/nih/Cerebral-magnetic-resonance-angiography/1355864.html
(13) http://www.ncbi.nlm.nih.gov/pubmed/12105357 
(14) http://www.ncbi.nlm.nih.gov/pubmed/12662190
(15) http://www.ncbi.nlm.nih.gov/pubmed/20655230
(16) http://archneur.ama-assn.org/cgi/reprint/66/6/704.pdf
(17) http://www.ncbi.nlm.nih.gov/pubmed/20534374
(18) http://www.ncbi.nlm.nih.gov/pubmed/22237929
(19) http://www.ncbi.nlm.nih.gov/pubmed/22285527

Menstrual Migraines

I. Menstrual Migraines is a hormone related headaches happened in the before, during or immediately after the period, or during ovulation as a result of the levels of estrogen and progesterone fluctuations in the menstrual cycle.

II. Symptoms
1. Headaches
2. Sensitivity to noise, light, smell or various combinations can worsen the headache
3.  Mood swing and fatigue
4.  Joints and muscles pain
5. Vomiting 
6. Scotomas
7. Nausea, backache, breast tenderness, and cramps.
8. Etc.

III. Causes
Menstrual migraines share many clinical characteristics of other types of migraines, but their occurrence is also give a woman a prediction of the coming of regular menstrual cycles
1. Hormone fluctuation
The drop of both hormones estrogen and progesterone in the final phase of the menstrual period must be in the harnomization state to prevent any disruption of the start of the first phase of the next menstrual cycle. In some women, because of the fluctuation of the hormones in the last stage, leading to menstrual headaches. Other researchers suggested that gonadal hormone fluctuation may influence both types of migraine(1)

2. Control pills
In the same report above, researchers also said women in the study who are taking oral contraceptive pill are also experience the aura symptom for the first time in the early cycles(1)

3.  Menopausal hormonal replacement therapy
Women who are in post-menopause stage, taken the hormonal replacement therapy to relieve the menopause symptoms are at higher risk of the development of menstrual migraine.

4. Periodic discontinuation of oral sex hormone preparations
Period discontinuation of oral sex hormone can cause fluctuation of hormones in the menstrual cycle of which may increase the risk of menstrual migraine.

5. OCs using
In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins, conducted by , J. W. Geothe University, there was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used, of which may enhance the risk of menstrual migraine(3)

6. First trimester of pregnancy
Migraine may worsen during the first trimester of pregnancy and, although many women become headache-free during the last two trimesters, 25p. 100 have no change in their migraine (Silberstein, 1997). MM typically improves with pregnancy, perhaps due to sustained high estrogen levels (Silberstein, 1997)(2)

7. Serotonergic tone
The estrogen withdrawal that occurs just prior to the onset of menses may lead to the loss of serotonergic tonewhich is thought to be the trigger for headaches that arise at this time of the menstrual cycle.(4)

8.  Etc.

IV. Types of menstrual migraine 
1. Pure menstrual migraine
Migraine attacks occur only around periods within the 2 days before a menstrual cycle or the first 3 days of menstrual bleeding, and not at other times, effecting approximate 1 in 7 women as the result of estrogen levels drop around the time of menstruation, of which causing pain to some women.

2. Menstrual-associated migraine
Migraine attacks not only occur around periods, but also at other times too, 6 in 10 women who have migraine have this type of pattern.

V. Diagnosis
A. Menstrual migraine shares symptoms of other types of migraine, but difference only in hyper in some symptoms but lessen in others.
Diagnosis of pure MM or menstrual related migraine according to the last International Headache Society classification, depending to the headache attack for migraine occurs exclusively on day 1 ± 2 of menstruation in at least two out of three menstrual cycles and at no other times of the cycle for Menstrual Migraine. Menstrually related migraine as headache occurs on day 1 ± 2 of menstruation in at least two out of three menstrual cycles and additionally at other times of the cycle.

B. Types of diagnosis
The aim of the diagnosis is to rule other causes of the diseases
1. CT scan
CT scan can dive your doctor a three-dimensional view of your bladder and the rest of your urinary tract to look for masses and other abnormalities that cause migraine headache

2. Magnetic resonance imaging (MRI)
By using radio waves and magnetic fields to take pictures, MRI scan provides very high quality of a cross-sectional slice and lengthwise slices of the brain and thus providing the better and detail image of location of tumor and the surrounding structures. It is one of most likely early test ordered by a doctor to diagnose tumors, strokes, aneurysms, neurological diseases and other brain abnormalities and the blood vessels around the brain.

3. Spinal tap (lumbar puncture)
A spinal tap is a procedure performed when a doctor needs to look at the cerebrospinal fluid (also known as spinal fluid), by inserting a thin needle between two vertebrae in your lower back to extract a sample. If your doctor suspects the onset of migraine headache is caused by inflammation of the membranes and cerebrospinal fluid surrounding your brain and spinal cord

4. Etc.

VI. Prevention
A. Do's and Do not's list, if you are experience menstrual migraine headache because of foods, food additives, chemical compounds, alcohol, smoking, stress, life style, etc.
1. Food elimination diet


Certain foods which trigger the over production of IgG antibodies if eliminated from the diet can result in the decreased number of migraine like headaches over 4weeks, some studies suggested that using the ELISA test with subsequent diet elimination advice significantly reduce the number of migraine like headaches at 4 weeks.(E.A.1)
2. Diet restriction
Diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks. In the study conducted by Istanbul Faculty of Medicine, Department of Neurology, Istanbul, Turkey in a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA(E.A.2)

3. Foods and chemical compounds trigger migraine headache
a. Certain foods can trigger the migraine headache attack through an allergic reaction. Citrus fruits, tea, coffee, pork, chocolate, milk, nuts, vegetables and cola drinks have been cited as possible allergens associated with migraine. If you are experience the attack after taking some of those, the best way is to avoid them. Researchers also suggested that substances are tyramine, phenylalanine, phenolic flavonoids, alcohol, food additives (sodium nitrate, monosodium glutamate, aspartame) and caffeine may be the cause of modifications in vascular tone and bring migraine on(E.A,3)
4. Alcohol
As we all known that a small dose of alcohol increase the protective effect on cardiovascular disease, but excessive drinking can increase the frequency of migraine headache as alcoholic drinks are a migraine trigger in about one third of patients with migraine in retrospective studies on trigger factors(E.A4)
5. Smoking
There is evidence that migraine was associated with several lifestyle and socioeconomic factors, In the investigation conducted by University of Copenhagen with a questionnaire containing validated questions to diagnose migraine and questions on lifestyle and socioeconomic factors was sent to 46,418 twin individuals residing in Denmark. 31,865 twin individuals aged 20-71 and most associations such as low education and employment status were probably due to the negative effects of having migraine while others such as smoking were risk factors for migraine.(E.A.5)

6. Others may trigger headache migraine attacks to certain people, such as
a. Too much work (Stress)
b. Too little sleep (Sleep related)
c. Passive smoking (Smoking)
d. Perfume (Chemical compound)
e. Etc.(E.A.6)
7. Moderate exercise
In a study of Forty women with general migraine attending the Neurology Department of the Faculty of Medicine Faculty of Dokuz Eylül University, regular long-term aerobic exercise is found in reduced migraine pain severity, frequency and duration possibly due to increased nitric oxide production.(A.E.7)

8. Management of migraine
Hygiene and behaviour measures capable of ensuring the best possible well-being (regular meals and balanced diet, restriction of alcohol and smoking, regular sleeping pattern, moderate physical exercise and relaxation) have found to reduce the frequent migraine attack(E.A.8)

9. Avoid medication overuse headache (MOH)
There are report that overuse of migraine medication can result of increased frequency to daily or near-daily as a rebound effect comes into play(E.A.9)

10. Balance intake of Omega 3 fatty acid instead of trans and saturated fat
Omega 3 fatty acid supports healthy estrogen metabolism and are a vegetarian great source of omega-3 fatty acids, while trans and saturated fat enhance the production of bad estrogen of which may contribute to hormone imbalance and the risk of menstrual migraines
11. Phytoestrogens
In the study of  the ten women who completed the study the average number of days with migraine during the baseline period decreased significantly after 3 months of therapy (P < 0.005). There were no major side-effects. Therapy did not affect cerebral blood flow velocities(7)
12. Etc.
B Nutritional Supplements for Migraine Headache
1. Magnesium
Some studies indicated that deficiency of magnesium is associated with patient with migraine headache as may promote cortical spreading depression, affecting serotonin receptor function, and influence synthesis and release of a variety of neurotransmitters and suggested that empiric treatment with at least oral magnesium is warranted in all migraine sufferers.(E.B.1)

2. Calcium
Calcium deficiency can lead to Hypocalcemia, a serum level of calcium that is below normal, it is manifested by increased neuromuscular irritability, leading to neuromuscular hyperexcitability, anxiety, dysautonomia, oculofrontal headache and migraine(E.B.2)

3. DLPA (DL-phenylalanine)
DL-phenylalanine, an essential amino acid of which is important for our body converts phenylalanine to tyrosine, another amino acid then to epinephrine and norepinephrine, which are important brain chemicals called neurotransmitters. Some researchers suggest that DL-phenylalanine (DLPA) appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain(E.C.9)

4. Vitamin B2
Riboflavin therapy supplemented may be appropriate alternatives in patients with migraine disorder as it significant decreases in headache frequency, intensity, duration and medication intake (E.C.7)

5. Melatonin
Serotonin, a type of neurotransmitter, passes messages between nerve cells, low serotonin levels in the brain may increase the risk of the process of constriction of the blood vessels as it alters levels of dopamine and stress hormones, and may be part of a complex cellular membrane trafficking dysfunction involving not only the serotonin transporter but also other transporters and ion channels of which trigger a migraine (B.A.7)

6. Coenzyme Q 10 (CoQ10)
In some studies found that deficiency of CoQ10 are common in pediatric and adolescent migraine, but determination of deficiency and consequent supplementation may result in clinical improvement and involving more scientifically rigorous methodology to confirm this observation.(E.B.3)

7. Omega 3 fatty acids Diet with long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of migraines in adolescents in astudy conducted by Divisions of Adolescent Medicine. Dr. Harel Z, and the team also sadi that results of this preliminary study suggest that both fish oil and olive oil may be beneficial in the treatment of recurrent migraines in adolescents. Further studies are warranted to compare each of these treatments with other interventions.(E.B.4)
8. Vitamin D and calcium
the is a report that intake of vitamin D and calcium has showed a major reduction in their headache attacks as well as premenstrual symptomatology within 2 months of therapy for two premenopausal women with a history of menstrually-related migraines and premenstrual syndrome in late luteal phase symptoms(5)
9. Etc.
C. Diet for Migraine headache
Certain diet may trigger the attack of migraine headache as a result of allergic reaction in certain people, but it may be helpful to people who are experience migraine headache with no allergic effects
1. Water
Water, an essential for the body’s proper functioning, and dehydration may trigger the migraine attack. Un a study of Fifty migraineurs were asked if insufficient fluid intake could provoke their migraine attacks conducted by The City of London Migraine Clinic, twenty replied "yes," 7 were doubtfully positive, and 23 said "no." In addition 14 of 45 migraineurs at a meeting of the British Migraine association (UK) also recognized fluid deprivation as one of their migraine triggers.(E.C.1) Adding fluid deprivation to migraine patient may reduce the numbers of migraine attacks.

2. Fish oil and Olive oil
Omega-3 PUFA, from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been studied to consist anti-inflammatory properties of which are useful in the management of inflammatory and autoimmune diseases, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches.(E.C.2)

3. Broccoli
Broccoli is a very good source of magnesium and a good source of calcium. Magnesium, plays an essential in many intracellular processes and in migraine pathogenesis, low levels of magnesium may promote cortical spreading depression, hyperaggregation of platelets, affect serotonin receptor function, and influence synthesis and release of a variety of neurotransmitters of which can trigger migraine headache(B.A.8)

4. Sardines
Sardines contain measurable amount of Omega 3 fatty acid, calcium and CoQ10 of which can be helpful in reducing the frequency of migraine headache (E.B.3)(E.B.2)

5. Spinach
Spinach is an excellent source of both calcium, magnesium, vitamin B2 (riboflavin)
Riboflavin therapy supplemented may be appropriate alternatives in patients with migraine disorder as it significant decreases in headache frequency, intensity, duration and medication intake (E.C.7)

6. Mustard Greens
The World's Healthiest Foods recommends mustard greens as an excellent source of calcium and a very good source of magnesium of which are important in preventing and treating migraine headache (See E.B.1 and 2)

7. Fish
Beside rich in Omega 3 fatty acids, all fish contain more or less DL-phenylalanine, an essential amino acid of which is important for our body converts phenylalanine to tyrosine, another amino acid then to epinephrine and norepinephrine, which are important brain chemicals called neurotransmitters. Some researchers suggest that DL-phenylalanine (DLPA) appears to potentiate pain relief and also ease depression in patients receiving opiates for chronic non-malignant pain(E.C.9)

8. Soy
Since falling levels of estrogen is the major provocative factor in migraine associated with menstruation. In the study of forty-nine patients were randomized to receive either placebo, or a daily combination of 60 mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, with each component standardized to its primary alkaloid, conducted by Department of Veterans Affairs Medical Center, patients received study medication for 24 weeks. Average frequency of menstrually associated migraine attacks during weeks 9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients to 4.7 +/- 1.8 (P < 0.01) in patients treated with the phytoestrogen preparation(6)
9. Etc.

For The World Most Healthy Foods, please visit http://healthy-foods-index.blogspot.ca/2011/03/healthy-foods-list.html
VII. Treatments in conventional medicine
 A. Types of therapy (Non medication treatment)
1. Hormone therapies
a. Estradiol supplements
In a review of the data from 35 women were available for a paired analysis. Percutaneous estradiol was associated with a 22% reduction in migraine days (RR 0.78, 95% CI 0.62 to 0.99, p = 0.04); these migraines were less severe and less likely to be associated with nausea. This was, however, followed by a 40% increase in migraine in the 5 days following estradiol vs placebo (RR 1.40, 95% CI 1.03 to 1.92, p = 0.03)(9)
b. Estrogen therapy
Falling estrogen levels or estrogen withdrawal after periods of sustained higher levels can trigger migraine, and hormonally associated migraine is a specific clinical entity. It is important to diagnose the type of migraine, considering the fact that a decline in estrogen level at the end of menstrual cycle triggers migraine, so it can be treated by low levels of estrogen.(11)
c. Combined oral contraceptives
In a study of women ages 20 to 35 years (n = 60) suffering from pure menstrual migraine without aura, conducted by University of Siena, showed a significant reduction in the intensity and duration of menstrual migraine, patients in group B (24/4 COC) reported a significant reduction in the intensity and a shorter duration of their menstrual migraine, compared with group A (21/7 COC)(12)

3. Biofeedback 
There are a report that the effects of biofeedback on patients suffering predominantly from either menstrual or nonmenstrual migraine is just as effective in reducing menstrual migraine as it is in reducing nonmenstrual migraine.(13)
4. Psychological and behavioral therapies
researchers at the IWK-Grace Health Centre suggested that Biofeedback, relaxation, and stress-coping treatments can be effective for the majority of migraine sufferers and treatment effects are reliably maintained for periods of at least one year, but little is known about the mechanism behind the efficacy of psychological treatments(14)

3. Etc.

B. Medication
B.A. Medication to relieve acute migraine pain
Depending to the severity of the disease, acute attacks may be best prescribed by a prescription version of an NSAID, of which have a potent vasoconstricting action (constricting blood vessels) and patients are instructed to take them during or at the onset of a mestrual migraine. including
1. Triptan
a. Triptan are a family of tryptamine-based drugs used in the treatment of migraine headache and cluster headache. In the comparison of subcutaneous sumatriptan and oral administration formulation, subcutaneous formulation has a faster time of onset and high rate of efficacy when compared with the oral formulation, but the oral formulation appears to be better tolerated.(F.B.A.1). Other study found that treatment of up to 12 perimenstrual periods over a 12- to 15-month period, the safety and tolerability of frovatriptan for short-term prevention of menstrual migraine was similar to that observed with acute use of triptans. Adverse events were generally mild or moderate in severity, there was no evidence of an increased risk of cardiovascular adverse events relative to acute treatment, and rebound headache was not evident. A short-term regimen with frovatriptan presents a safe and viable treatment option for preventing predictable migraine such as menstrual migraine(8)
In other study,  Zolmitriptan 2.5 mg oral tablet is effective and well tolerated as a short-term preventative therapy for menstrual migraine attacks(10)
 b. Side effects of Triptan are not limit to
b.1. Nausea
b.2. Dry mouth
b.3. Tingling
b.4. Burning,
b.5. Dizziness
b.6. Drowsiness
b.7. Warm or cold sensations
b.8. Feelings of heaviness, pressure, or tightness
b. Other severe symptoms include coronary spasm, heart disease, shortness of breath, changes in vision, etc.

2. Ergotamine
Ergotamine has been used to treat migraine for a century and is still considered to be the most effective therapeutic agent for acute attacks andt good responses of the medication are associated with plasma concentrations of 0.2 ng/ml or above within one hour of administration.
In the same study, researchers also emphasized the principal adverse effects of ergotamine include nausea, vomiting, weakness, muscle pains, paraesthesiae and coldness of the extremities and suggested dosage must therefore be limited to no more than 10mg per week to minimise toxicity.(F.B.A.2)

3. The oral calcitonine gene-related peptide antagonist telcagepant
In a recent study conducted by University of Liège, in comparison of the oral calcitonine gene-related peptide antagonist telcagepant(CGRP) and triptans, found that its efficacy is almost comparable but its tolerance is superior. The same is true for the 5HT-1F agonist lasmiditan, another agent devoid of vascular effects. Researchers also said that the drugs with a better efficacy or side-effect profile than triptans may soon become available for acute treatment. The future may also look brighter for some of the very disabled chronic migraineurs thanks to novel drug and neuromodulation therapies.(F.B.A.3)

4. Etc.

B.B. Medication to prevent migraine pain
Medication used to prevent migraine pain are normal prescribed for patient who are experience frequent migraine attacks, severe side effects from acute treatment drugs or ineffectiveness of acute treatment drugs and together with behavioral therapy and lifestyle adjustments.
1. Beta-blocker (usually propranolol [Inderal] or timolol [Blocadren])
a. Beta-blocker are also known as beta-adrenergic blocking agents, use to block norepinephrine and epinephrine from binding to beta receptors on nerves to prevent migraine headache. Some researchers suggested that the addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment.(F.B.B.1)
b. Side effects are not limit to
b.1. Beta-blocker may interact with other medicines, such as thioridazine, chlorpromazine, etc.
b.2. Most common side effects include dastrointestional discomfort such as stomach cramps, nausea and vomiting.
b.3. The medication may also increase nervous symptoms, including headache, depression, confusion, dizziness, etc.
b.4. Etc.

2. Anticonvulsants (usually divalproex [Depakote] or topiramate [Topamax])
a. Anticonvulsants or anti seizure are medication used to treat epileptic seizures, bipolar disorder as mood stabilizers and neuropathic pain. In the study conducted by Department of Neurology, Canisius Wilhelmina Ziekenhuis, anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days compared with placebo, and more than double the number of patients for whom migraine frequency is reduced by > or = 50% relative to placebo.(F.B.B.2).

b. Side Effects are not limit to
1. The medication may also increase central nervous symptoms such as dizziness, drowsiness, unsteadiness, feeling dull difficulty concentrating, focusing, mood swing, etc.
2. The medicine may cause gastrointestinal discomfort such as nausea, and vomiting.
3. Other side effects include liver or kidney damage and decrease the amount of platelets in your blood
4. Etc.

3. Tricyclic antidepressants (usually amitriptyline [Elavil])
a. Tricyclic antidepressants are also known as cyclic antidepressants, a chemical compound used to treat depression by affecting chemical messengers, neurotransmitters, in the brain. In the study conducted by Ohio University, Athens, found that amitriptyline is more effective than placebo for migraine and tension headache. Amitriptyline also seems to be more effective than serotonin reuptake inhibitors, although few direct comparisons are available.(F.B.B.3)

b. Side Effects are not limit to
b.1. The medication may cause central nervous symptoms, such as blurred vision, confusion, drowsiness, etc.
b.2. Loss of sexual desire
b.3. Lowered blood pressure
b.4. Tremors and sweating
b.5. Etc.
The doses and duration is depending to the nature of the migraine, but in general, patient started the medication at a low dose, and then gradually increased.
   
V.III. In herbal medicine  
1. Peppermint
Peppermint contains high amounts of menthol which have long been used in herbal medicine to treat various pain conditions including headache. In a randomised, triple-blind, placebo-controlled, crossed-over study conducted in the neurology Clinic of Nemazee Hospital, affiliated with Shiraz University of Medical Sciences, Shiraz, southern Iran, from March 2007 to March 2008. Menthol solution can be an efficacious, safe and tolerable therapeutic option for the abortive treatment of migraine(G.1)

2. Feverfew
Feverfew and it's ingredient parthenolide have shown the inhibition of the brain chemicals that dilate blood vessels and cause a migraine. Some researchers suggested that a CO(2)-extract of feverfew decreased the migraine frequency from 4.76 by 1.9 attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group (P = 0.0456). Logistic regression of responder rates showed an odds ratio of 3.4 in favour of MIG-99 (P = 0.0049). Adverse events possibly related to study medication were 9/107 (8.4%) with MIG-99 and 11/108 (10.2%) with placebo (P = 0.654). MIG-99 is effective and shows a favourable benefit-risk ratio.(G.2) while others insisted that there are insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine.(G.3)

3.
Butterbur
Butterbur is a creeping underground plant, genus Petasites of 15 -20 species, belonging to the family Asteraceae, native to Northern Hemisphere. In a comparison in a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine conducted by Albert Einstein College of Medicine, Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine.(G.4)

4.
Ginkgo biloba
Ginkgo biloba is oldest living tree species, genus Ginkgo, belonging to the family Gink-
goaceae, native to China. Some researchers suggested that Gingkolide B, a herbal constituent extract from Ginkgo biloba tree leaves, seems to be effective as preventive treatment in reducing migraine attack frequency and in attenuating the use of symptomatic medication in our small series of children with primary headache in a small sample of 30 young patients(G.5). Other found that Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second(G.6)

5. Cannabis
Cannabis is a herbal plant with three putative varieties Cannabis sativa, Cannabis indica and Cannabis ruderalis, native to Central Asia, and South Asia. clinical cannabis indicated that Migraine has numerous relationships to endocannabinoid function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors supporting therapeutic efficacy in acute and preventive migraine treatment. Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects. AEA is tonically active in the periaqueductal gray matter, a migraine generator and suggested that Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns share an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines(G.7)

6. Lavender
Herbalist suggested that rubbing a little lavender oil on your temples, or dropping some in the bath water can be extremely soothing. For the migraine associated with depression or poor digestion, it may be result of the relaxation and coronary circulative effects of the oil(G.8)
7. Soy, Dang Qui and Black Cohosh
Since falling levels of estrogen is the major provocative factor in migraine associated with menstruation. In the study of forty-nine patients were randomized to receive either placebo, or a daily combination of 60 mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, with each component standardized to its primary alkaloid, conducted by Department of Veterans Affairs Medical Center, patients received study medication for 24 weeks. Average frequency of menstrually associated migraine attacks during weeks 9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients to 4.7 +/- 1.8 (P < 0.01) in patients treated with the phytoestrogen preparation(6)

7. Others
Many herbs such a Fenugreek, Black willow, Marjoram, St. John's wort, fennel or caraway seed tea hane been used to relieve pain or symptoms of migraines, but they are not mention here because lack of studies.

For information of The World Most Popular Herbs - Health Benefits and Side Effects, visit
http://theworldmostpopularherbs.blogspot.ca/2011/10/world-most-popular-herbs-health.html
IX. In traditional Chinese medicine (TCM) 
 H.A. According to Flaws & Sionneau, 2001,p.346; Yin & Liu, 2000, p.370; Blackwell, 1991 Migraine Headache is as a condition of tou feng (Wind in the head) or pian tou tong(pain in one half of the head), and is mainly due to emotional factors causes of Liver Yang hyperactivity and sometimes may be influenced by exterior Wind-Cold factors, common cold and allergy(H.A.). In the report the author indicated that differetiation of the MH depending to the patient’s pathology and the pathodynamics underlying any particular clinical case is likely to be complex. As pain is the single most important clinical feature, Blood stasis should beaddressed in all cases. Thus, one of the formulas described under thesubheading of Blood Stasis will be included in all acute stage treatments. In addition, Interior Wind is also a common feature and this often occurs due to Liver Fire or stagnant Heat in the Liver. In some cases there is also Phlegm,which binds with Wind to exacerbate the symptoms.(Part 2MIGRAINE HEADACHE IN TCM)

According to the differentiation above, Menstrual migraine is a result of blood stasis but it may accompany with other causes included below and formulas described under the subheading of Blood Stasis will be included in all acute stage treatments.
1. Symptoms
a. Fixed pain,
b. Palpitation
c. Pulse appears tense and fast
d. Tongue is purple -
f. bluish-purple

2. Formula for migraine headache caused by blood stasis
2.1. Tao Hong Si Wu Wan (Persica, Carthamus & Dang-gui Combination)
The formula has been used in TCM to treat heavy bleeding of dark, purplish, sticky menstrual blood  sharp and fixed abdominal pain before or during the menses, dizziness, dull headache, etc. as a result of blood stasis
a. Shu di huang (Rehmannia glutinosa root-prep)
b. Dang gui (Angelica sinensis root)
c. Bai shao (Paeonia lactiflora root)
d. Tao ren (Prunus persica seed)
e. Hong hua (Carthamus tinctorius flower)
f. Chuan xiong (Ligusticum wallichii rhizome)

2.2. Tong Qiao Huo Xue Wan (Tong Qiao Huo Xue Teapills)
a. Chi shao (red peony) - invigorates the blood, dispels blood stasis, clears heat, cools the blood, and clears Liver fire. Tranquilizing, analgesic, anticonvulsive, and coronary artery-dilating. 
b. Chuang xiong (ligusticum) - useful for all types of headaches, invigorates blood, expels wind, and alleviates pain. Antispasmodic, tranquilizing, hypotensive, and vasodilative. 
c. Cong bai (green onion/scallions) - disperses cold, unblocks yang, and relieves toxicity. Sudorific, antipyretic, and expectorant. 
d. Da zao (jujube) - tonifies spleen, nourishes blood, harmonizes herbs, and reduces toxicity. Anti-allergic. 
e. Hong hua (safflower) - invigorates blood, dispels blood stasis, and alleviates pain. Hypotensive and dilates coronary arteries. 
f. Sheng jiang (fresh ginger) - warms the middle jiao and alleviates vomiting, and reduces toxicity of other herbs. Anti-emetic, stomachic, sudorific, and vasodilator. 
g. She xiang (musk) - opens orifices, invigorates blood, reduces swelling, and alleviates pain. CNS stimulant, hypotensive, and anti-inflammatory. 
h. Tao ren (peach kernel) - breaks up blood stasis, especially in menstrual disorders. Anticoagulant, hypotensive, antiphlogistic, and analgesic (15)


H.B. Migraine headache caused by Liver Yang rising with Interior Wind
1. Symptoms
a Visual disturbance
b. Dizziness
c. Irritability
d. Red tongue
e. Wiry pulse
f. Etc.

2. Formula Liver Yang rising with Interior Wind - Tian Ma Gou Teng Yin
a. Gastrodia and Uncaria formula has been used in TCM for hundred of years to treat the symptoms of headache and migraine as a result of ascendant Liver Yang with internal movement of Wind, caused by Liver and Kidney Yin deficiency and exuberant Liver Yang. This formula is best used during the early stages of a Migraine and combines well with Corydalis H for a strong, double strike against Migraine pain.

b. The ingredients including
b.1. Tian Ma (Rhizoma gastrodiae elatae)
b.2. Gou Teng (Ramulus cum uncis uncariae)
b.3. Shi Jue Ming (Concha haliotidis)
b.4. Zhi Zi (Fructus gardeniae jasminoidis)
b.5. Huang Qin (Radix scutellariae baicalensis)
b.6. Yi Mu Cao (Herba leonuri heterophylli)
b.7. Chuan Niu Xi (Radix cyathulae officinalis)
b.8. Du Zhong (Cortex eucommiae ulmoidis)
b.9. Sang Ji Sheng (Ramulus sangjusheng)
b.10. Ye Jiao Teng (Caulis polygoni multiflori)
b.11. Fu-shen (Sclerotium poriae cocos pararadicis)

H.C. Liver Fire
1. Symptoms
a. Red face and eyes
b. bitter taste in the mouth
c. thirst
d. dark and scanty urine
e. constipation with dry stools
f. red tongue with a yellow coat
g. rapid pulse

b. Formula Long Dan Xie Gan Tang
The formula Long Dan Xie Gan Tang has been used in TCM to treat pain in the hypochondriac region, headache, dizziness, red sore eyes, trouble with hearing, ear swelling or infection, traveling the Liver and Gallbladder meridians to relieve liver heat and fire
b.1. Long dan cao (Radix gentianae longdancao)
b.2. Huang qin (Radix scutellariae)
b.3. Shan zhi zi (Fructus gardeniae jasminoidis)
b.4. Ze xie (Caulis mutong)
b.5. Mu tong (Semen plantaginis)
b.6. Che qian zi (Rhizoma alismatis orientalis)
b.7. Chai hu (Radix bupleuri)
b.9. Sheng di huang (Radix rehmanniae glutinosae)
b.10. Gan cao (radix glycyrrhizae uralensis)
b.11. Dang qui (Radix angelicae sinensis)
Author note the formula may damage the Kidney due to the presence of Herb Mu Tong

H.D. Liver qi stagnation
1. Symptoms
a. Chest distention
b. Hypochondriac pain
c. Nausea, vomiting
d. Poor appetite
e. Diarrhea
f. Depression
g. Mood swing
f. Normal tongue
g. Wiry pulse
h. Etc.

2. Formula as a result of Liver Qi deficiency: Xiao Yao San (Bupleurum and Dang-gui Formula)
The formula has been used in TCM to treat anxiety, irritability, stress, and depression due to the challenge of a daily life or premenstrual tension, as a result of liver Qi deficiency
a. Chai Hu (radix burpleuri)
b. Dang Gui (radix angelicae sinensis)
c. Bai Shao (radix paeoniae lactiflorae)
d. Bai Zhu (rhizome atractylodis macrocephalae)
f. Fu Ling (sclerotium poriae cocos)
g. Zhi Gan Cao (honey fried radix glycyrrhizae uralensis)


H.E. Excess syndrome-pattern with Liver Blood stasis:
1. Symptoms
a. Palpable masses in the abdomen
b. Irregular a/or painful menstruation possible with dark clots,
c. purple nails,
d. purple lips
e. Tongue Purple, possibly w/purple spots
f. Wiry pulse

b. Formula for Excess syndrome-pattern with Liver Blood stasis: Chai Hu Shu Gan Tang
The formula has been used in TCM to treat sighing and flank pain due to emotional stress or premenstrual tension, headache as a result liver Blood stasis.
a. Chai hu (Radix Bupleuri Chinensis)
b. Chen pi (Pericarpium Citri Reticulatae)
c. Bai shao (Radix Paeoniae Lactiflorae)
d. Zhi ke (Fructus Aurantii)
f. Chuan xiong (Rhizoma Ligustici Chuanxiong)
g. Xiang fu (Rhizoma Cyperi Rotundi)
h. Gan cao (Radix Glycyrrhizae Uralensis)

H.F. Headache Migraine caused by Wind Phlegm
1. Symptoms
a. Excessive sputum
b. Nausea,
c. Fullness of the chest and/or epigastrium
d. Greasy tongue coat
e. Etc.

2. Wind Phlegm With Heat (if tongue is red tongue with a yellow coat): Wen Dan Tang (Bamboo & Hoelen Formula)
The formula has been used in TCM to treat disharmony between the gallbladder and stomach causes of Qi is blocked in flow transformed phlegm and form of rebellion Qi in the stomach that lead to fear, restlessness, dreaminess and anxiety
a. Zhi Ban Xia (Rhizoma Pinelliae Ternatae)
b. Zhu Ru (Caulis Bambusae In Taeniis)
c. Chen Pi (Pericarpium Citri Reticulatae)
d. Fu Ling (Poriae Cocos)
f. Lian Qiao (Fructus Forsythiae Suspensae)
g. Jin Yin Hua (Flos Lonicerae Japonicae)
h. Yu Jin (Radix Curcumae)
i. Zhi Shi (Fructus Aurantii Immaturus)

3. Formula Wind Phlegm With Cold (if tongue is pale with a white coat): Er Chen Wan (Citrus & Pinellia Combination), ingredients include
The Formula has been used in TCM to treat nausea and abdominal fullness, dizziness and vertigo, etc., as a result of Withe Phlegm with cold causes of phlegm accumulation, spleen-damp, rebellion qi and unharmonization of the center.
a. Chen Pi (Pericarpium Citri Reticulatae)
b. Ban Xia (Rhizoma Pinelliae)
c. Fu Ling (Poriae Cocos)
d. Gan Cao Glycyrrhiza (Radix Glycyrrhizae Uralensis)
f. Sheng Jiang Zingiberis (Rhizoma Zingiberis)

H.G. Invasion by Exterior Wind Cold
1. Symptoms
a. Generalized body aches
b. Aversion to cold
c. Chills
d. Mild fever
e. Nasal congestion
f. Thin white coat
g. Floating, possibly a little tight

2. Formula for mihraine headache caused by Invasion by Exterior Wind Cold: Chuan Xiong Cha Tiao Wan (Ligusticum & Tea Formula)
The formula has been used in TCM to treat headache, migraine, or headache on the top, aversion to cold and fever, dizziness, nasal obstruction as a result of Exterior Wind Cold
a. Bo he (Herba Menthae Haplocalycis)
b. Chuan xiong (Rhizoma Ligustici Chuanxiong)
c. Jing jie (Herba Schizonepetae Tenuifoliae)
d. Qiang huo (Rhizoma Seu Radix Notopterygii)
e. Bai zhi (Radix Angelicae Dahuricae)
f. Gan cao (Radix Glycyrrhizae Uralensis)
g. Fang feng (Radix Saposhnikoviae Divaricatae)

Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/7641250
(2) http://www.ncbi.nlm.nih.gov/pubmed/11139745
(3) http://www.ncbi.nlm.nih.gov/pubmed/12521654 
(4) http://www.ncbi.nlm.nih.gov/pubmed/17044842 
(5) http://www.ncbi.nlm.nih.gov/pubmed/8002332
(6) http://www.ncbi.nlm.nih.gov/pubmed?term=soy%20and%20menstrual%20migraine
(7) http://www.ncbi.nlm.nih.gov/pubmed/15190238
(8) http://www.ncbi.nlm.nih.gov/pubmed/19788471
(9) http://www.ncbi.nlm.nih.gov/pubmed/17190936
(10) http://www.ncbi.nlm.nih.gov/pubmed/18788838
(11) http://www.ncbi.nlm.nih.gov/pubmed/18265590
(12) nhttp://www.ncbi.nlm.nih.gov/pubmed/21843889
(13) http://www.ncbi.nlm.nih.gov/pubmed/2030078
(14) http://www.ncbi.nlm.nih.gov/pubmed/8761710 
(15) http://www.acupuncturetoday.com/mpacms/at/article.php?id=31253
(E.A.1) http://www.ncbi.nlm.nih.gov/pubmed/21835022
(E.A.2) http://www.ncbi.nlm.nih.gov/pubmed/20647174
(E.A.3) http://www.ncbi.nlm.nih.gov/pubmed/8681169
(E.A.4) http://www.ncbi.nlm.nih.gov/pubmed/21336550
(E.A.5) http://www.ncbi.nlm.nih.gov/pubmed/21390550
(E.A.6) http://www.ncbi.nlm.nih.gov/pubmed/20847084
(E.A.7) http://www.ncbi.nlm.nih.gov/pubmed/12971707
(E.A.8) http://www.ncbi.nlm.nih.gov/pubmed/20464586
(E.A.9) http://www.ncbi.nlm.nih.gov/pubmed/20464586
(F.A.1) http://www.ncbi.nlm.nih.gov/pubmed/9127120
(F.A.2) http://www.ncbi.nlm.nih.gov/pubmed/9673806
(F.B.A.1) http://www.ncbi.nlm.nih.gov/pubmed/22272067
(F.B.A.2) http://www.ncbi.nlm.nih.gov/pubmed/3899452
(F.B.A.3) http://www.ncbi.nlm.nih.gov/pubmed/21464715
(F.B.B.1) http://www.ncbi.nlm.nih.gov/pubmed/20880898
(F.B.B.2) http://www.ncbi.nlm.nih.gov/pubmed/18454787
(F.B.B.3) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3273735/?tool=pubmed
(F.B.C.1) http://www.ncbi.nlm.nih.gov/pubmed/17878396
(F.B.C.2) http://www.ncbi.nlm.nih.gov/pubmed/16324164
(F.B.C.3) http://www.ncbi.nlm.nih.gov/pubmed/11554957
(G.1.) http://www.ncbi.nlm.nih.gov/pubmed/20456191
(G.2.) http://www.ncbi.nlm.nih.gov/pubmed/16232154
(G.3.) http://www.ncbi.nlm.nih.gov/pubmed/14973986
(G.4.) http://www.ncbi.nlm.nih.gov/pubmed/15623680
(G.5) http://www.ncbi.nlm.nih.gov/pubmed/21533745
(G.6) http://www.ncbi.nlm.nih.gov/pubmed/19415441
(G.7) http://www.ncbi.nlm.nih.gov/pubmed/18404144
(G.8) http://www.ncbi.nlm.nih.gov/pubmed/17689755
(H.A.) http://www.tonyreidtcm.com.au/downloads/clinical_articles_and_review/MIGRAINE%20HEADACHE%20PART%202.pdf
(H.B.) http://maxnature.stores.yahoo.net/garewifoandu.html